Jeremy BarryJeremy M. Barry

Assistant Professor, Neurological Sciences

PhD, SUNY Downstate 2008

Jeremy.Barry@uvm.edu


 

Research

During my career I’ve carved out a unique niche bridging basic and translational science. I’ve used a systems neuroscience approach toward studying the neurophysiological basis of spatial learning and memory and the origins of cognitive deficits in animal models of pediatric seizures. The culmination of this work has been the proposal of temporal coordination theory, which proposes that dynamic organization of cell activity by theta oscillations within and between neural circuits is necessary for normal cognition. I’ve shown that temporal coordination of hippocampal place cell activity is disrupted as a long-term consequence of seizures experienced in early life, correlating with spatial cognitive deficits. Recent work suggests preempting transcriptional factor changes following pediatric seizures or using anti-microtubulin agents in an ASD model can improve cognitive outcomes on spatial tasks.  Rectifying the microstructure alterations in developmental disorders has the potential to improve the coordinated timing in neural circuits and local rhythms like theta and gamma that underpin learning and memory. These experiments also show that both early-life seizure models and ASD models are fruitful ground for testing causal relationships between temporal discoordination in neocortical-hippocampal circuits and spatial cognitive impairment. I have also become recognized for pushing against technical boundaries in neuroscience research by: 1) Characterizing the electrophysiological properties of propagating action potentials along axons in freely moving animals; 2) Being the first to manipulate behavioral and cognitive state toward the study of optogenetic stimulation efficacy in the septo-hippocampal circuit of wild-type rats; 3) Designing tools for optogenetic stimulation in rat pups; and 4) Utilizing high-density, or multi-site electrophysiological probes for the interrogation of neocortical-hippocampal circuits in developmental disorders.  My work involving the titration of cognitive demand, in conjunction with in vivo optogenetics, has served as a foundation for an NIH grant that will further test the necessity of temporal coordination for spatial cognition and incorporate closed-loop optical interfaces with hippocampal circuit physiology. This research aims to correct pathological spike timing changes caused by early-life insults and delineate the role of circuit state and cognitive demand in endogenous or artificial oscillation entrainment.

Jeremy Barry
UVM NBH Forum platform presentation 2018

Peer Reviewed Publications

Original Research

1.  Holzer, M., Schmitz, C., Pei Y, Graber, H., Abdul, R.A., Barry, J.M., Muller, R., and Barbour, R. (2006). 4D functional imaging in the freely moving rat. Conference proceedings :  Annual International          Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Conference 1:29-32. PMID: 17945970.

2. Fenton, A.A., Lytton, W.W., Barry, J.M., Lenck-Santini, P.P., Zinyuk, L.E., Kubík, S., Bures, J., Poucet, B., Muller, R.U., and Olypher, A.V. (2010). Attention-like modulation of hippocampus place cell discharge. J. Neurosci (13): 4613-25. PMCID: 2858227.

3. Barry, J.M., and Muller, R.U. (2011). Updating the hippocampal representation of space: Place cell firing fields are controlled by a novel spatial stimulus. Hippocampus 21(5), 481-494. PMID: 20087890.

4. Barry, J.M., Rivard, B., Fox, SE, Fenton, A.A., Sacktor, T.C., and Muller, R.U. (2012). Inhibition of PKMzeta disrupts the stable spatial discharge of hippocampal place cells in a familiar environment. J. Neurosci, 32(40):13753-62. PMCID: 3752127.

5. Jenks, K.R., Lucas, MM, Duffy, B.A., Robbins, A.A., Gimi, B., Barry, J.M., and Scott RC. (2013). Enrichment and training improve cognition in rats with cortical malformations. PloS one 8:e84492. PMCID: PMC3866176.

6. Robbins, A.A., Fox S.E., Holmes, G.L., Scott, R.C., and Barry, J.M. (2013). Short duration waveforms recorded extracellularly from freely moving rats are representative of axonal activity. Frontiers in neural circuits 7:181. PMID: 24348338.

7. Hernan, A.E., Alexander, A., Jenks, K.R., Barry, J.M., Lenck-Santini, P.P., Isaeva, E., Holmes, G.L., and Scott, R.C. (2014). Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits. Neurobiology of disease 63:25-34. PMID: 2426973.

8. Holmes, G.L., Tian, C., Hernan, A.E., Flynn, S., Camp, D., and Barry, J.M. (2015). Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide. Neurobiology of disease 77, 204-219. PMID: 25766676.

9. Barry, J.M.*, Choy, M.*, Dube, C., Robbins, A., Obenaus, A., Lenck-Santini, P.P., Scott, R.C., Baram, T.Z., and Holmes, G.L. (2015). T2 relaxation time post febrile status epilepticus predicts cognitive outcome. Exp Neurol 269, 242-252. PMID: 25939697.

10. Barry, J.M., Tian, C., Spinella, A., Page, M., and M, Holmes, G.L. (2016). Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands. Epilepsy Behav 60, 1-6. PMID: 27152463.

11. Barry, J.M., Sakkaki, S., Barriere, S.J., Patterson, K.P., Lenck-Santini, P.P., Scott, R.C., Baram, T.Z., and Holmes, G.L. (2016). Temporal Coordination of Hippocampal Neurons Reflects Cognitive Outcome Post-febrile Status Epilepticus. EBioMedicine 7, 175-190. PMID: 27322471.

12. Blumberg, B., Flynn, S., Barriere, S., Mouchati, P., Scott, R., Holmes, G.L., and Barry, J.M. (2016). Efficacy of non-selective optogenetic control of the medial septum over hippocampal oscillations: the influence of speed and implications for cognitive enhancement. Physiological Reports 4(23). PMID: 27923975.

13.  Barry, J.M.*, Patterson, K., Curran, M., Singh-Taylor, A., Page, M., Noam, Y., Holmes, G.L., and Baram, T.Z. (2017). Enduring Memory Impairments Provoked by Developmental Febrile Seizures Are Mediated by Functional and Structural Effects of Neuronal Restrictive Silencing Factor. J Neurosci Apr 5;37(14):3799-812. PMID: 2827519.

14. Mouchati, P.R., Barry, J.M., and Holmes, G.L. (2019) Functional brain connectivity in a rodent seizure model of autistic-like behavior. Epilepsy Behav, 95:87-94. PMID: 31030078

15. Barry, J.M., Mahoney, M.J., and Holmes, G.L. (2020). Coordination of hippocampal theta and gamma oscillations relative to spatial active avoidance reflects cognitive outcome after Febrile Status Epilepticus. Behavioral Neuroscience 134:562-576. PMID: 32628031.

16. Mouchati, P., Kloc, M., Holmes, G.L., White, S., and Barry, J.M. (2020). Optogenetic ‘low theta’ pacing of the septo-hippocampal circuit is sufficient for spatial goal finding and is influenced by behavioral state and cognitive demand. Hippocampus PMID: 32710688.

17. Kloc, M., Velasquez, F., Niedecker, R.W., Barry, J.M., and Holmes, G.L. (2020). Disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition. Brain Stimulation 29; 13(6): 1535-1547. PMID: 32871261.

18. Niedecker, R.W., Kloc, M.L., Holmes, G.L., and Barry, J.M. (2021). Effects of early life seizures on coordination of hippocampal-prefrontal networks: Influence of sex and dynamic brain states. Epilepsia 62(7):1701-14. PMID: 34002378.

19. Kloc M.L, Daglian, J.M., Holmes, G.L., Baram, T.Z., and Barry, J.M. (2021). Recurrent febrile seizures alter intrahippocampal temporal coordination but do not cause spatial learning impairments. Epilepsia 62(12):3117-30. PMID: 3456202.

20. Kloc, M.L., Marchand, D.H., Holmes, G.L., Pressman, R.D., and Barry, J.M. (2022). Cognitive impairment following experimental febrile seizures is determined by sex and seizure duration. Epilepsy Behav 126:108430. PMID: 34902661.

21. Getz, S., Tariq, K., Marchand, M., Dickenson, C., Howe, J., Skelton, P., Wang, W., Li, M., Barry, J.M., Hong, J., Luikart, B. (2022). PTEN Regulates Dendritic Arborization by Decreasing Microtubule Polymerization Rate. J. Neurosci - In press.

Review Articles

1. Barry, J.M. (2015). Axonal activity in vivo: technical considerations and implications for the exploration of neural circuits in freely moving animals. Frontiers in neuroscience 9:153. PMID: 25999806.

2. Barry, J.M., Holmes, G.L. (2016). Why are children with epileptic enecephalopathies enecephalopathic? In press: Journal of Child Neurology. PMID 27515946.

Books and Chapters

1. Book Chapter:  Barry, J.M., and Holmes, G.L. (2019). Neurobiology of cognitive impairment in developmental epilepsy: Seeing the forest through the trees. In: “Developmental Epilepsy: From Clinical Medicine to Neurobiological Mechanisms” edited by Carl Stafstrom and Libor Velisek for World Press.

In Preparation:

1. Dickson, C.R., Holmes, G.L., and Barry, J.M. Dynamic Theta Frequency Coordination Within and Between the Prefrontal Cortex-Hippocampus Circuit During Learning of a Spatial Avoidance Task. eNeuro – 1st Resubmission

2. Kloc, M.L., Daglian, J.M., Holmes, G.L, Baram, T.Z., and Barry JM. Spatial learning impairments and entorhinal-hippocampal circuit discoordination post experimental Febrile Status Epilepticus.

 

Current Lab Members:

Honors Thesis Student: Anthony Spinella

Anthony Spinella

Current Project: In Vivo characterization of hippocampal electrophysiological processes in the heterozygous Pten knockout model of autism
Co-Supervisor: Matthew Weston

Research Assistant: Rhys Niedecker

Rhys Niedecker

Current Project: The role of septo-hippocampal circuit dynamics in the optogentic entrainment of hippocampal oscillations

Undergraduate Student Volunteer: Rose Warren

Biomedical Engineering Program

Lab Alumni:

  • Ellen Wixted, Summer Neuroscience Undergraduate Research Fellowship (SNURF), Neuroscience PhD student at the University of Michigan
  • Matias Page, Honors College Thesis Student, Undergraduate Neuroscience Program, Medical Scribe at the Larner College of Medicine
  • Bailey Holt-Gosselin, Summer Neuroscience Undergraduate Research Fellowship (SNURF), Research Assistant at Stanford University
  • Kate Van Pelt, Summer Neuroscience Undergraduate Research Fellowship (SNURF), Senior Neuroscience Student at Oberlin College
  • Philippe Mouchati, Research Assistant, Master of Science Program in Biotechnology at Northeastern University