Niitiggya

Hello everyone!

My name is Niitiggya and I am a junior in the honors college majoring in human biology. I am part of the Upstate Accelerated Scholars program and I will be matriculating to SUNY Upstate for medical school after graduating from UAlbany. In my free time, I enjoy working out and going on scenic drives.

I joined the Scimemi lab in spring 2022 to learn more about Alzheimer’s. To my surprise, I learned more than I thought imaginable in such a short period of time. Over the last four months, I performed stereotaxic surgeries, PCR, and perfusions. To be able to see a project through all the way from the characterization of a young mouse’s genotypes to an analysis of its cortical tissue has been a rewarding experience. The first project I worked on was understanding the role of amyloid-beta plaques in synaptic transmission in the CA1 region of the hippocampus. I injected a viral vector bilaterally into the hippocampus and performed a perfusion of the brain to analyze hippocampal slices after 3 weeks. While I read about this procedure multiple times in textbooks, to see perform it in person expanded my knowledge of the subject tenfold. Aside from lab skills, I learned a great deal about data collection and analysis. I learned how to not only interpret data, but to also convey my findings to an audience. I am so grateful for my time in the Scimemi lab thus far and I cannot wait for all that I will learn over the upcoming semesters!

Niitiggya Taneja

And then came graduation time!

Hello everyone,

My name is Saad Ahmad, and I am a graduating senior at SUNY Albany. I have been an undergraduate researcher in the Scimemi Lab since freshman year in 2018. I have recently completed my honors thesis on the Circadian Modulation of Astrocyte Morphology and Synaptic Transmission. I would like to extend my gratitude to everyone in the Scimemi Lab for supporting me through my undergraduate research career, as without their help I would never have been able to complete an honors thesis. Furthermore, the Scimemi Lab has been instrumental in helping me develop skills that I would not have been proficient in with just classwork. From learning PCR in my freshman year to performing image analysis with Imaris, they have been consistently patient and encouraging despite my many mistakes. One of the most valuable lessons I have learned through my undergraduate career is to own up to my mistakes and understand why they happened. By doing this, I gained a better understanding of procedures and troubleshooting steps. The lab also frequently hosted speakers and attended seminars together so I knew if I didn’t understand something there would be others to lean on for help.

My future career goals are to attend medical school and eventually become a physician. While I prepare my application, I will be working with Dr. Jaqueline Burre and Dr. Manu Sharma at the Appel Alzheimer’s Disease Research Institute. I hope to continue to expand my interest in neuroscience and research during my gap year and hopefully carry the skills I learn over into my career as a physician.

Saad

Corey

Hi!

I am Corey Nilon and I am about to finish my third year here at SUNY Albany. I am pursuing a Bachelor’s in biology and have minors in sociology and neuroscience. I originally joined the Scimemi lab in Fall 2020 and have happily been here for two years now! In my free time, I like to be outdoors, play sports, and travel.

In Fall 2020, I started learning polymerase chain reaction and the process of genotyping. Now, for over the last year, I have been focusing on the behavioral aspect of the EAAC1 project. With the help of others in the lab, I was able to truly organize and design my own experiment. I was  knee-deep in each part of the project- it’s planning, data collection, analysis, and conclusions. While there have certainly been many bumps in the road, I am thankful for them, as they’ve directly contributed to my learning. Overall, I would say this experience so far has been incredible. My knowledge of scientific theory, experimental design, general motor behaviors, and neuroscience have all expanded significantly. I presented my research on behavior twice this semester, first at the 19th Annual Student Conference and then at the Biology Undergraduate Symposium. This were my first experiences creating a scientific poster and presenting my research- it was awesome. Of all I’ve learnt in college, these have definitely been among the most rewarding experiences I’ve had.

Going forward, I am excited to build upon my studies by trying something new- computational neuroscience. This summer, I will be interning at the lab and I’ll be taking my first dive into astrocyte imaging/modeling and analysis through programs like Imaris. I look forward to trying something new!

Sarah

  

   Hello everyone!

    I am Sarah Anderson, I am just about to finish my junior year here at SUNY Albany. I am currently working towards a Bachelor’s in Science with a double major in biology and psychology! I joined the team as an undergraduate research assistant in September of 2021 and it has been an incredible experience thus far! I will continue to gain experience in the Scimemi lab throughout the rest of 2022 and into 2023. This research has expanded my knowledge of neuroscience tenfold and continues to be a learning experience.

    Being a member of the Scimemi lab has been such a great experience. From the moment I joined this lab, everyone has been incredibly welcoming and always willing to help one another out. This was very reassuring, as I had done all of my previous biology labs virtually, I was nervous that the hands-on work would present a tough learning curve. However, with the support of everyone within the Scimemi lab, the transition from virtual to in-person was made relatively easy.

    Throughout the fall 2021 semester, I was learning PCR and the proper way to maintain the mouse colony by backcrossing the mice to prevent genetic drift. Towards the end of the fall semester, I began to focus on other projects that were being done by Gabrielle Todd. During the spring 2022 semester, I had transitioned to helping Gabrielle perform a dot blot that compares the glutamate transporter concentrations in wild type and Aß mice at different age cohorts. By learning each step of the complex process from Gabrielle, I was eventually able to perform protein purifications, Bradford assays and dot blots almost entirely independently. I was fortunate enough to get to present my research in the 39th Annual Biological Sciences Research Symposium. This event broadened my horizons to the range of research that is being conducted here at SUNY Albany, and it was overall a really fun event!

    The opportunity that Dr. Scimemi gave me by letting me become one of the undergraduate researchers in her lab is priceless, I have learned so much and will continue to actively learn until I graduate! I can’t wait to be a part of the Scimemi lab for another year!

Sarah Anderson

Mustafa

Hello everyone!

My name is Mustafa Muhi, a Junior Biology major at SUNY Albany. I joined the Scimemi lab in January 2022 and have been working since then. I enjoy reading, traveling, playing video games, and playing soccer. Since I joined the Scimemi I have learned a wide variety of skills ranging from learning to do literature reviews, write papers, PCR, and the ability to scientifically approach challenges that I may face. At the start of my time in the lab, I learned how to handle the mice colonies and genotype the mice through PCR. Although at that time I was very inefficient at those tasks and often needed help, with the help of everyone in the lab I became very efficient and comfortable with my roles. As the lab received the new mouse strains mice, I began with optimization of their PCR protocol. This required me to combine everything I have learned throughout the semester. Although I am still working on some protocol optimization, I hope I could eventually create an efficient protocol for people to use in the future. I have learned so much in the time I have been in this lab, I plan to continue to be a part of the lab this semester and next year. I hope to be able to learn how to do stereotaxic brain surgeries and to be more involved in the lab. I cannot wait to learn more from all the kind people in the Scimemi lab!

Mustafa

Garrett

 

Hi everyone!

   My name is Garrett Wagner, and I am about to graduate here at SUNY Albany with a Bachelor’s in Science in Biology and a minor in Neuroscience. I joined the Scimemi lab in July of 2021 hoping to further my knowledge on how certain mechanisms work within the brain.

   From my interview with Dr. Scimemi, before I even began, I knew that her current work would be quite fascinating to learn.  I began my time in the lab learning PCR as well as how to take care of the mouse colony. In the fall of 2021, I began working with Nurat Affinih and Monica Rodriguez to analyze mouse brain images to determine the effects that the loss of the glutamate transporter, EAAC1, has on dopaminergic cell survival within the mouse midbrain.  My role involved using programs such as Fiji to count the dopaminergic cells and determine regions of interest such as the VTA and SNc.  I also began to familiarize myself with Igor which was used for analysis of our cell count totals and create figures to present our data in a more reasonable format.  Those figures were then included in my presentation at the 39th Annual Biological Sciences Undergraduate Research Symposium.  I valued this opportunity greatly as I gained more experience in presenting to others. 

   From my time in the lab, I have learned so much in just a short period of time.  I’ve gained a much better understanding of how research is performed and the time and effort it takes from everyone in the lab.  As I continue my journey following undergrad, I plan to take a gap year and apply for medical school.  I look forward to continuing my time in the Scimemi Lab this summer as well as other opportunities that may come about. 

Garrett

Jaci

Hello! 

My name is Jaci Yong and I am a sophomore at the University at Albany majoring in Psychology and minoring in Neuroscience. I joined Dr. Scimemi’s neuroscience research lab as a volunteer from Fall 2021 to Spring 2022. After attending one of Dr. Scimemi’s virtual seminars in the Honor’s College during my freshman year about glutamate transporters and the mechanisms that control neurotransmitter release and information transfer among neurons, I became very interested in her research and wanted to get involved with it. Later that summer, the Center for Undergraduate Research and Creative Engagement sent out an email saying that Dr. Scimemi was looking to recruit 2 undergraduate students to join her lab in Fall 2021, so I filled out an application, was interviewed, and then accepted into the lab.

As a student who was spending my first year in college learning remotely from home, I felt a bit isolated from the campus community and from research opportunities, which is a big reason why I wanted to get involved in research as soon as I was able to go to campus in-person. I had never worked in a research lab previously, so my first day touring the lab felt a bit intimidating, but I met a lot of great people in the lab who were eager to share their work with me and explain things that I was unsure about. 

In Dr. Scimemi’s research lab, I shadowed PhD student Ben Bennink for my first semester and was trained in mouse colony management and behavior analysis. I worked with the other new undergraduate student, Stephanie Fischer in running behavioral experiments with different groups of mice. Having never worked with animals in a research setting, working with mice (especially newborn mice) took some getting used to, but eventually as I worked with them more frequently and they got older, I became a lot more comfortable. Another challenge I faced was learning how to run software such as MATLAB and Igor Pro for data collection and analysis. I had very little knowledge about technology and coding before this lab, but after becoming more familiar with these programs, I have definitely learned a lot more and I am still learning more new things every day! I have applied to continue conducting behavior research in the 2022-2023 academic year under the Honors Psychology Department and I am excited to explore more aspects of neuroscience research in this lab as well!

Hasan

Hello reader!

My name is Hasan Mehdi and I am an upcoming senior at the University at Albany, pursuing a BS in Biology. I joined the Scimemi lab in the summer of my junior year and have been here ever since!
In my free time, I love playing videogames, ping pong, and basketball. I also love hiking.
Doing research at the lab has taught me a wide range of skills that I never would have imagined. Over the summer, I was taught how to care for a mice colony by Gabrielle Todd as well as genotype them using the polymerase chain reaction. I watched and performed stereotaxic brain surgeries with Patrick Wehrle and learned how to read and present research papers to the rest of the lab. During the school year, I worked with Saad Ahmad and learned the software side of neuroscience, using programs like Imaris to reconstruct confocal images of astrocytes and dendrites, and Igor to conduct density analyses and compile our raw data into figures to present in papers and posters. I also learned how to use Fiji to perform a simple neurite tracer analysis to create figures of all the neurons we analyzed and observed and conducted mouse perfusions with Saad.
Being at the lab has kept me busy. Just in the last couple weeks I presented our poster Dendritic spine morphology changes following stereotaxic injections of A𝛽42-AAV for the 39th Annual Biological Sciences Undergraduate Research Symposium and the CURCE 19th Annual Student Conference. In the future, I want to combine my love of Biology with the world of coding, in the Bioinformatics field. This summer I have been accepted to do a Bioinformatics fellowship at the RNA Institute to get some direct experience with the field.

Hasan

Nikki's life in the lab

Welcome to our neuroscience blog everyone! 

My name is Nikki Dolphin and I am a senior here at the University of Albany finishing my Bachelor's degree in biology this spring! I first became interested in Dr. Scimemi’s neuroscience lab during my junior year after reading her previous research work and laboratory interests. I have always been interested in neuroscience and learning ways to apply certain laboratory skills in order to learn new things about the brain caught my eye. I came with little to no background about caring for or working with our laboratory animal models, mice. During my first week I was brought up to speed and certified to work them. I first initially shadowed another undergraduate student, Nurat, who was preforming surgeries. Later, I learned my role in the lab. I now have been working with different mice colonies for two years and have been put in charge of running our behavioral experiments (I even get to name them!). But of course, with fun also came a lot of work that I was unfamiliar with. I was also responsible for becoming very tech savvy with Igor and MATLAB, both software's I had never even heard of. I was really pushed out of my comfort zone and expected to perform was during this time I really grasped onto my love research and the obstacles that it came with. In addition, we also had weekly lab meetings which I believed were really helpful and knowledgeable. It was during these meetings I was also able to learn about what my peers in the lab were researching and how it pertained to my work. Not only that but we also took turns presenting on various academic journals which gave me a great opportunity to sharpen my reading and presenting skills while also learning something new. 

I hope to attend graduate school in the future to further my research skills and become my own independent researcher!

Nikki

Saad's comment on "Region specific astrocyte subtypes"

Astrocytes are glial cells that tile the nervous system and have complex morphology characterized by multiple branch levels and fine processes. Astrocytes have been regarded as largely identical until recently despite having a large degree of functional diversity. Batiuk et al (2020) explored the molecular diversity of astrocytes using single-cell RNA sequencing. Astrocytes were divided into 5 subtypes (AST1-5) based on the expression of 886 highly variable genes with AST5 being the least abundant (1.4%) and AST1 being the most abundant (36.5%). Furthermore, some subtypes are localized to specific brain regions as AST1 and AST4 are predominantly hippocampal while AST2 is mainly cortical. While some genes are expressed across all subtypes over 70% of enriched genes are specific to a subtype. AST4 was linked to neurogene sis as the enriched genes in this subtype show involvement in mitosis, cell cycle control, transcriptional regulation, neurogenesis, and neuronal differentiation. While AST5 showed considerable overlap with AST4, it was also enriched in genes coding for traditional astrocyte functions such as glucose metabolism. AST1-3 were grouped together as they all showed gene enrichment profiles indicating mature astrocyte function. AST1 showed a distinct specialization in synaptogenesis, synaptic plasticity, and glutamatergic neurotransmission. After establishing the molecular differences among astrocytes, Batiuk et al (2020) looked to explore morphological differences. They found smaller territorial volume in AST2 and 3 which are localized in cortical layers 2-4 when compared to AST3 which is localized to the hippocampal CA3 region. Going forward, it may be interesting to see more studies correlating the transcriptome to morphology and function as we learn more about region-specific astrocytes.

Saad

Reference

Batiuk, M.Y., Martirosyan, A., Wahis, J. et al. Identification of region-specific astrocyte subtypes at single cell resolution. Nat Commun 11, 1220 (2020). 

Hello everyone!

My name is Danielle Saint Hilaire and I am a Senior Biology Major and Neuroscience Mnor. I joined the lab last semester (Fall 2020) and have been really enjoying it! On my first day, I learned all about what Polymerase Chain Reaction (PCR) is, and since then it has been my primary job in the lab, along with colony management. In my short time here in the lab, I have learned more than I thought possible in just a few months. As a new member in the lab, I got acquainted with the various mouse genotypes and the different projects being worked on; I learned quickly that determining the genotype of the mice is an imperative first step to any experiment. So I dove right in. I learned how to decide which genes to type for and I also learned how to follow the extensive protocol for preparing the samples for PCR. I found it really fascinating how I could collect the DNA samples and see it through all the way until we got the final product: the genotype. Aside from technical skills, being a member of the lab has taught me so much about how to analyze scientific literature. In our weekly lab meetings, we rotate (from PhD students, to Masters students, to Undergrads), and we all take turns choosing, dissecting, and presenting a new and cutting edge research article. When I presented my first paper, I remember having to do so much research behind the scenes of the various data collection techniques (as a newly declared Neuroscience Minor, my background in lab techniques was, let’s say, lacking). Not only dissecting these papers for myself, but hearing others from the lab contribute has been so critical in learning how to consume research papers; most papers aren’t as ‘black and white’ as they seem, if you look deep enough, you’ll find a lot of grey areas too. Another unexpected benefit of working in the lab has been overcoming my dislike of public speaking. Before joining the lab, if I was asked to present to the class or share my thoughts, I would’ve high-tailed it in the other direction. But working in the lab and discussing papers in lab meetings/presenting my work at research conferences has made all the difference. And now I actually love presenting - what a reversal! It’s great to be passionate and knowledgeable about a topic and be able to share it with others. Working in the lab has been, by far, my favorite experience at UAlbany. I’ve been able to work with a wonderful group of passionate, focused people, and have been able to learn from them throughout it all. Not only that, but I’ve also been able to contribute to a project that’s bigger than me, that will, hopefully, one day make a difference for someone living with a neurodegenerative disease or OCD.

Danielle

Hello everyone!

My name is Corey Nilon, and I am a sophomore studying Biology with minors in Neuroscience and Sociology. Last semester, because of COVID-19, I was only a virtual member of the lab. This has been my first semester coming to the lab in person and I have enjoyed every part of it. It is a great educational environment to be in and it is so fascinating to see all the projects that people around me are working on! So far, my experience in the lab has been a significant amount of ezTrack data analysis, mouse colony management, and PCR. ezTrack is a Python-based program that I have been using to track the location and trajectories of mice and they perform reward-based motor tasks. Furthermore, going forward, I plan to use this program to note differences in behavior relative to differences in various genes. By studying these mice, we hope to gain insight into the neural circuits controlling behaviors similar to that of obsessive-compulsive disorder. 

Outside of the lab, I am the president of the Special Olympics club and a part of the TriBeta honors society. I also have been volunteering at Albany Medical Center since last Fall, which has been an extremely rewarding experience being able to have primary interactions with all types of medical personnel: doctors, nurses, technicians, and patients. 

I am proud to be a part of the lab as it is a great opportunity to contribute to real-life science. It is very different from most other sciences classes where you're only learning material and things that have already been, for the most part, figured out. The experimental side of science is a pleasure to be a part of, and I look forward to being a part of future discoveries!

In the future, I have hope to attend medical school. From there, I am excited to see where life takes me!

Corey

Ian's synopsis on: "Glutamate signaling and plume characteristics in a genetic mouse model of migraine with aura" by Parker et al.

Migraine is a neurological disorder that commonly consists of symptoms such as extreme headaches and sensory amplifications. It is commonly associated with aura, which is characterized by spreading sensory hallucinations (flashing visual perceptions, numbness, and tingling). Spreading depolarization (SD) is known to be the underlying cause of migraine aura. Familial hemiplegic migraine type 2 (FHM2) is a form of migraine with aura that arises from loss-of-function mutations to the gene ATP1A2 (the gene encoding the predominantly astrocytic alpha2 Na+/K+-ATPase). Astrocytes in heterozygous FHM2 mice show slower uptake kinetics of glutamate due to a 50% reduction in the concentration of glutamate transporter GLT-1a in perisynaptic astrocyte processes. This serves as an effective mouse model for migraine with aura. How this astrocytic mutation reshapes glutamate signaling in awake FHM2 mice is largely unknown. Here, they use the fluorescent glutamate reporter iGluSnFR to measure glutamate in FHM2 and WT mice. They found that FHM2 mice exhibited spontaneous glutamatergic “plumes” that were generally circular in nature and appeared to spread from a central origin. Plumes occurred predominantly in superficial cortical layer 1 (L1a), and much less frequently in deeper L1b and L2/3. This correlated with the density of GLT1a+ astrocyte processes, as L1a exhibited a reduced density of these processes as compared to L2/3, and superfusion of the glutamate transporter inhibitor TFB-TBOA caused a large number of plumes in L1a, leading the researchers to believe that plumes are a result of impaired glutamate uptake. Glutamate release during plumes is likely due to Ca2+-mediated vesicular release from neurons. Once glutamate is released, the presence of plumes is gated by impaired or inefficient glutamate clearance by astrocytes. Plumes tend to occur during the depolarization phase, following the glutamatergic wavefront commonly seen in SD and rises in glutamate and plume frequency predict the onset of SD. This links plumes to the key translational phenotype of FHM2 and all other models of migraine with aura.

Ian

Reference 

Parker, P. D., Suryavanshi, P., Melone, M., Reinhart, K. M., Sawant-Pokam, P. A., Kaufmann, D., Theriot, J. J., Pugliese, A., Conti, F., Shuttleworth, C. W., Pietrobon, D., Brennan, K. C. (2020). Non-canonical glutamate signaling in a genetic model of migraine with aura. NEURON, 109(4), 561-740. doi:10.1101/2020.01.02.891770

Dopamine triggers rise in intracellular calcium concentration in astrocytes and depresses excitatory synaptic transmission in the nucleus accumbens

Dopaminergic inputs to the nucleus accumbens (NAc), originating in the ventral tegmental area, are key for motor control and reward. Previous reports suggested that dopamine reduces excitatory synaptic transmission by acting on presynaptic D1 receptors, and by altering adenosine signaling. What remains unknown is how dopamine changes the functional properties of NAc astrocytes. Given that various neurotransmitters increase the intracellular calcium concentration in astrocytes, Corkrum et al.  hypothesize that dopamine may be able to evoke similar effects.

To test this hypothesis, Corkrum et al. used a combination of transgenic mice, optogenetics and pharmacogenetics to show that dopamine evokes a rise in the intracellular calcium concentration in NAc astrocytes by activating D1 dopamine receptors. The work is based on the use of elegant controls, like those relying on the use of astrocyte-specific deletion of D1 dopamine receptors. Dopamine also impairs excitatory synaptic transmission through signaling pathways that rely on activation of presynaptic A1 receptors in NAc neurons. The hypothesized chain of events include a rise in intracellular calcium concentration evoked by activation of D1 receptors in astrocytes that promotes ATP/adenosine release from these cells. Adenosine binds to presynaptic A1 receptors in neurons, thereby reducing excitatory synaptic transmission.

Since dopamine is also implicated with drug addiction, the authors analyzed the effects of the amphetamine, a psycho-stimulant known to disrupt dopamine release, re-uptake and degradation. Just like dopamine, amphetamine increased the intracellular calcium concentration in astrocytes evoked by dopamine release, and inhibited excitatory transmission.

These findings are important because they show that astrocytes modulate excitatory glutamatergic transmission in the NAc by responding to changes in dopamine release. Therefore, future strategies to understand the molecular basis of addiction, should take into account the contribution of these cells to the regulation of synaptic strength.

Saad Ahmad and Nikhita Kumar

Reference

Corkrum M, Covelo A, Lines J, Bellocchio L, Pisansky M, Loke K, Quintana R, Rothwell PE, Lujan R, Marsicano G, Martin ED, Thomas MJ, Kofuji P, Araque A (2020). Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity. Neuron 105(6):1036-1047.e5.

Perforated patch clamp recordings reveal new facets of dopaminergic modulation of striatal neurons

Dopaminergic neurons in the substantia nigra projecting to the basal ganglia nucleus of the striatum control movement initiation and acceleration. This effect is thought to be mediated by altering the cell excitability of the two main types of long-projection neurons in the striatum, which differ for their expression of either D1 or D2 dopamine receptors. In previous studies, the effect of dopamine has been investigated using reduced preparations (i.e. brain slices) and by analyzing the biophysical properties of striatal medium spiny neurons using whole-cell patch clamp recordings and by mimicking dopamine release through exogenous applications. Whole-cell patch clamp recordings disrupt the physiological composition of the intracellular milieu, as the solution of the patch pipette dialyzes the intracellular cytoplasm. In addition, the exogenous application of dopamine may not recapitulate the physiological time course of dopamine release in vivo. As a result, there are conflicting results on how D1 dopamine receptor activation alters cell excitability in striatal medium spiny neurons. Here, Lahiri and Bevan combine perforated-patch recordings from D1 medium spiny neurons (MSNs) with optogenetic stimulation of dopamine release from nigro-striatal afferents to the dorsolateral striatum. They show that dopamine release increases the firing rate of D1-MSNs elicited by long domatic current injections, which mimic up-states. This effect persists for more than 10 min and is mediated by PKA activation. To mimic both up and down states, the authors apply 250 ms current steps once a second for 41 seconds, a protocol that they applied every 5 minutes for 3-4 trials. Based on the fact that the latency to action potential firing decreases and the firing frequency increases during optogenetic stimulation, they conclude that dopamine promotes the transitions from down to up states. Through the use of a wide range of pharmacological assays, they show that dopamine reduces the fast and medium after-hyperpolarization, consistent with an effect on slowly inactivating A-type potassium channels and calcium activated potassium channels. Together, this extensive array of heroic experiments shed light on previously unknown molecular mechanisms  through which the firing output of MSNs responds to changing levels of extracellular dopamine. Although the optogenetic stimulation of nigro-striatal afferents used by the authors may not capture aspects of asynchrony in dopamine release from nigro-striatal afferents, this is the closest we have got to understand the molecular machinery regulating the complex functional properties of striatal neurons.

Ian Tschang and Sam Barron

Reference
Lahiri AK, Bevan MD (2020). Dopaminergic transmission rapidly and persistently enhances excitability of D1 receptor-expressing striatal projection neurons. Neuron (xx), xxx–xx.

Example of three patch clamp configurations

Dopaminergic neurons from the VTA and SNc control movement reinforcement

The work presented in this manuscript aims to determine how dopaminergic midbrain neurons contribute to movement reinforcement and movement generation. To address this, the authors used in vivo optogenetics to activate halorhodopsin (eNpHR3.0) expressed in the ventral tegmental area (VTA), the region containing the cell body of mesolimbic dopaminergic neurons. They subjected mice to a Pavovian paradigm, in which they paired a conditioning olfactory cue with an unconditioned sweetened milk reward. After training, the olfactory cue triggered an anticipatory licking that began before reward delivery. Light inhibition of VTA neurons reduced this anticipatory licking (which occurs in the time window between cue presentation and reward delivery) more than consummatory licking (which occurs after reward delivery) and this effect scaled with reward size. Together, these results suggest that dopaminergic neurons control movement reinforcement more than generation. In subsequent experiments, they show that post-reward inhibition of dopaminergic neurons in the substantia nigra pars compacta (SNc) also inhibits anticipatory licking, suggesting that dopaminergic neurons in these two brain regions might have overlapping functions. Through a series of fiber photometry measures of GCaMP6f fluorescence, they showed that dopaminergic neurons are active both before and after reward delivery, with post-reward dopamine neuron activity regulating learning. These findings are important because they support the hypothesis that VTA and SNc neurons both contribute preferentially to movement reinforcement rather than generation, although they do not rule out the possibility that specific subsets of dopaminergic neurons may have specialized roles in controlling specific features of the movement execution process. 

Nikki Dolphin and Anna Tuttman

Reference
Lee K, Claar LD, Hachisuka A, Bakhurin KI, Nguyen J, Trott JM, Gill JL and Masmanidis SC (2020). Temporally restricted dopaminergic control of reward-conditioned movements. Nat Neurosci (23), 209–16.

The striatal way of encoding information about locomotor speed

Movement execution relies on the activity of the striatum, but there are current unknowns on how the striatum selects actions and controls their speed. The “discrete encoding model” posits that striatal neurons generate a burst of activity at the beginning and the end of a movement. By contrast, the “continuous encoding model” posits that striatal neurons fire continuously during movement execution, to encode information about the sensory and/or motor state of an animal. In this work, the authors tested the validity of these two models. They performed experiments in which they obtained single and multi-unit recordings from the dorsomedial striatum of mice in an open field. By analyzing neuronal firing rates during bouts of locomotor activity, they showed that 18% of all recorded units increased their firing near the start of locomotion, and 15% of them increased firing near the end of it. The changing in firing rates in these cohorts of neurons reflected changes in locomotor speed. A close comparison of the firing activity of striatal neurons during head-fixed and free-moving locomotion suggest that the speed representation features of most striatal neurons may show continuous changes in firing rates and might be context-dependent. One of the main caveats of in vivo experiments on head-restrained mice is that the vestibular inputs are not comparable to those of freely moving mice. In addition, we wondered whether the results might change depending on the selection criteria used to identify neurons that encode locomotor information (as opposed to other types of movements like grooming, rearing or digging). Therefore, this interpretation holds for locomotor activity at speeds greater than 5 cm/s, it may or may not hold true for at slower speeds. Future works may shed light on the behavior of striatal neurons over all ranges of speed.

Nurat Affinnih and Haley Chesbro

Reference
Fobbs WC, Bariselli S, Licholai JA, Miyazaki NL, Matikainen-Ankney BA, Creed MC, Kravitz AV (2020). Continuous representations of speed by striatal medium spiny neurons. J Neurosci 40(8):1679-1688.

Genotyping: the gateway to the lab

Hello everyone!

My name is Sam Barron and I am a Sophomore studying biology. This is currently my first semester in the lab, and I have had a great time so far. Coming in, I did not have a very strong background in neuroscience, so I was unsure as to how well I would fit in the lab. However, I have learned so much and everyone in the lab has been very helpful. It is a great environment that anyone can be a part of and excel in.

As the new member in the lab, I have spent most of my time getting on par with genotyping our mouse colony using polymerase chain reactions (PCR). Despite being a bit repetitive, it is a great way to become acquainted to the lab and the different mouse genotypes that are used. While on the topic of PCR, I would like to direct your attention to its developer: Kary Mullis. He won the Nobel Prize in Chemistry in 1993 for developing the technique, which changed the study of biology forever. He has also been one of the most controversial and polarizing figures in the scientific community. From denying AIDS and global warming to describing an encounter with aliens, Mullis has exhibited radical beliefs in science. His basis for these ideas stem from his belief that many scientists and corporations are motivated by money and personal success over using science to better the world. While there may be flaws in his views, it is important that we as scientists work for others and not ourselves. If you want to read more about Mullis I recommend his autobiography Dancing Naked in the Mind Field.

Outside of the lab, I am a part of the UAlbany Men’s Ultimate Frisbee team and Tri Beta Biological Honors Society. I also spend time playing the piano and volunteering at the StrattonVA Medical Center.

Being in the lab has and will provide valuable learning experiences as I look towards the future. After I graduate, I hope to go to medical school. I hope to become a neuropathologist where I can do research and help those with different neurological diseases.

Sam Barron

Venturing from informatics to neuroscience

Greetings, listeners of the Neurovoice! 

My name is Jesse Parent and I’m a graduating Informatics senior in Dr. Scimemi’s Neuroscience lab. I am actually a non-traditional 'transfer' student who went back to school for a STEM career change. I originally came to UAlbany because it was an online-only degree and I had to work during the day. Fortunately, I had a flexible enough to work and slowly gain more research experience over time, and upon recommendation I found my way into this lab. I started last semester in the Fall.

My first outreach at the Brain Awareness Day 2018 at Bethlehem High School (Delmar, NY)

What an experience it has been! I would encourage anyone interested in cross-disciplinary research or applying computer science or informatics to biology to try it out. A lab like Dr. Scimemi's is open and welcoming and there are a lot of different ways to contribute - even if you have little background in Neuroscience. I wasn't sure how much real biology I would touch upon during my time in the lab; when I showed up, there was strange looking grey box and some parts to assemble and I spent several months setting up that hardware and related software. But the neuroscience was there: my first project involved using custom telemetry for electroencephalograms (EEG) to interpret brain activity in mice.

Our lab at the 2018 Society for Neuroscience Hudson-Berkshire Chapter Meeting (Scotia, NY)

One of my favorite things about undergraduate research is that the learning is much more raw, and real. It's a challenge, and sometimes (or a lot of times) you are dealing with questions that nobody knows the answer to - unlike your typical classroom lecture. But you have to stay humble and persistent. I was humbled often by thinking I had solutions that weren't solutions, and I had no way of knowing they weren't solutions until I asked the right question. Sometimes you won’t know which question is helpful - but it's OK! That's part of the process; just keep communicating where you are along the way - this was one of my first Big Lessons. 

Not being a natural science major, I gained a lot of respect with real life challenges of "doing science", and having to know the "full stack" of science. That is, having to know the ‘why’ at all of the different levels, from where to put electrodes, to how the signal is transmitted and converted into what the software reads out, how to process that data to illustrate what we're looking at, why we're looking at this subject specifically, and how all of this relates to a particular issue within the field. A formative experience was my first lab report, an in-house presentation of what had done so far in the lab. During your first life science presentation, you make mistakes and learn a lot. There's a precision and familiarity that comes with each specific field of study, and I've only touched upon what that is in neuroscience. It has been like painting: setting a primer coat on for the first time - a bit messy, but I feel confident about building upon it in the future. Experiences like this really make undergraduate research worth it, in my opinion. 

I have been a part of research teams in four different departments on campus (which actually my secondary agenda for coming to UAlbany; previous institutions I attended did not have this diversity in undergraduate research opportunities). If you are at all considering doing research, I must encourage you to do so. The Center for Undergraduate Research and Creative Engagement (CURCE) has really developed nicely and its staff are exceedingly helpful. I actually received two grants from CURCE for some of my other independent research projects! If you are interested in biology and neuroscience, definitely check out Scimemi Lab. When your PI gives you room to try and fail, explore, and is willing to invest in you as a student and cares about your career future, it makes a big difference in your lab experience and how you feel about the subject matter.

The best mentors and PIs will help you capture enthusiasm while helping you get a lay of the land, and I really wish everyone can experience that in their undergraduate studies. It changes how you view understanding, how you see yourself in the process of education, and gives you a glimpse of how hard it is to build knowledge. Maybe, like me, you discover you like this process and want to work at contributing to the what knowledge we have. Having great labmates around you help, too - which was a part of this lab experience for me. Previously, I worked one-on-one or in isolated pairings, but this open lab atmosphere and ability to communicate and be next to others “in the trenches” - it was really my favorite environment so far. There are overlapping, interesting projects, and some of the best moments are the side conversations that offer perspective and insight into other’s situations - or at least commiserating about The Struggle of science!

My secondary project involves setting up an open-sourced MySQL-based database to automate some of the downstream computations involved in processing large batches of data. Being able to work with new software, hardware, databases, documentation, talking with creators/inventors of devices, and trying to relate all of this understanding functionally to the lab has absolutely been challenging, but it has also been great training and exposure to lab life. Of course, it is a lot of fun, too; it lets you feel like you are voyaging out on the great sea of understanding, and you have your role, your mission and you have to play your part. You have good days and bad days in the lab, but that's all part of the journey.

I wish I started sooner so I'd have more time in the lab and get more experience in a biology environment. It has helped me solidify that I want to take my informatics training towards biology, rather than leaning purely towards computer science. Particularly, the area of computational cognitive neuroscience or the computation that underpins cognition and information processing. I hope to pursue graduate research on that topic, and will be involved in summer research on representational brains and phenotype, modeling neural development.

Outside of the lab, I’ve worked on research projects in Informatics (Autonomous Systems and Machine Learning), Cybersecurity, and Electrical & Computer Engineering (Human-Robot Interaction); I’ve been involved in student tech groups such as IEEE, ACM & ACM-W, ASIS&T; UAlbany Students Stopping Trafficking & Exploitation of People (SSTEP); and e-NABLE (simple prosthetic hands for those in need). I also frequently bothered folks via departmental list servs about cool events such as Princeton Envision Conference, Machine Intelligence Conference, Ethics of AI, or New York Celebration of Women in Computing. There’s are many quality opportunities locally (and Dr. Scimemi is a great facilitator of opportunities for you to develop your skills and provide outreach for the community). Get involved! 

Feel free to connect on Twitter @JesParent, and good luck on your journey of understanding!

Jesse Parent

Microetching neurons with Gabrielle!

Greetings! My name is Gabrielle and I am the Scimemi Lab Manager. I have a BA in Biology from Cornell University, a PhD in Chemical Biology from the University of Michigan and several years of post doc experience. My expertise lies in molecular biology, although I have dabbled in NMR, mass spectrometry, biochemistry and microscopy. I have worked in a wide range of organisms from plants to bacteria to viruses, but the Scimemi lab marks my inauguration into mammalian research. Managing a mouse colony can be challenging as there are a lot of moving parts, but it is a fun organization/optimization problem. While I have no formal training in neurobiology, it is exciting to be able to apply my molecular biology skills to a new field.

I recently came across a ScienceFriday interview with the artist Greg Dunn. He uses a technique called photolithography to make detailed artwork of neurons. He draws neurons with ink, scans the image and prints microetching data at ultrahigh resolution onto a transparency to generate a mask. He places these masks onto a photoresist surface and shines UV light over it. Wherever UV light penetrates the mask, it polymerizes the photoresist material, which hardens it; regions shielded by the mask do not polymerize and can be washed away with a basic solution. The remaining features are subsequently plated in gold leaf. This microetching process generates features with single micron resolution (or about 1/100 of the width of human hair!).

Intriguingly, in addition to creating beautiful two dimensional images, Dunn has also incorporated animations into his microetched patterns such that as a light source is moved over the image (or when your perspective changes) the reflection of light from the gold leaf fluctuates to portray electrical signals travelling across the neurons. He has used this technique to generate an image of a slice of the entire brain, incorporating real scientific data about the size of ~500,000 neurons and their features, the connectivity between different parts of the brain, and information about the coordination among firing neurons during 500 microseconds of “brain time”. These exquisite images serve to highlight the complexity and the stunning beauty of our brains. More artwork can be found here. Enjoy!

Gabrielle Todd