National Institutes of Health
Weizmann Institute of Science
Degree: Doctor of Philosophy in Biophysics
University of California
Degree: Bachelor of Science in Biochemistry
Modulation of Synaptic and Extra-Synaptic Plasticity
Long term changes in rapid electrical signaling between neurons (plasticity) may be a mode of memory storage within our brains. Memory acquisition, retention and learning is influenced by various neurological and neuropsychiatric conditions. My laboratory is focused on elucidating functional changes in signaling and circuitry in different parts of the brain as a result of normal aging, or as a result of neuropsychiatric disease such as depression or neurological disease such as epilepsy. We use electrophysiological techniques combined with optogenetics and mouse models to measure changes in postsynaptic potentials as well as action potentials in the prefrontal cortex and hippocampus. The hippocampus is associated with spatial and temporal learning and memory, while the prefrontal cortex is involved in higher brain function including facets of memory and attention. Among the projects currently running in the laboratory are:
Cognitive Impairment in Epilepsy - What changes in circuitry occur in the hippocampus as a result of generation of an epileptic state? What effect does generation of the epileptic brain have on the ability to induce long-term plastic changes in communication between neurons?
Cognitive Impairment in Depression - Lack of Serotonin is associated with a clinically depressed state, as SSRIs (selective serotonin reuptake inhibitors) can be used as anti-depressants. How does serotonin affect neuronal communication? Is the ability to cause long term changes in plasticity influenced by serotonin.
Other projects are also available.
Harms JE, Benveniste M, Kessler M, Stone LM, Arai AC, Partin KM. A charge-inverting mutation in the "linker"
region of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors alters
agonist binding and gating kinetics independently of allosteric modulators. J Biol Chem. 2014 Apr 11;289(15):10702-14. doi: 10.1074/jbc.M113.526921. Epub 2014 Feb 18. PMID: 24550387
Inagaki A, Frank CA, Usachev YM, Benveniste M, Lee A. Pharmacological correction of gating defects in the voltage-gated Ca(v)2.1 Ca²⁺ channel due to a familial hemiplegic migraine mutation. Neuron. 2014 Jan 8;81(1):91-102. doi: 10.1016/j.neuron.2013.10.056. PMID: 24411734
Ehlen JC, Jefferson F, Brager AJ, Benveniste M, Paul KN. Period-amplitude analysis reveals wake-dependent changes in the electroencephalogram during sleep deprivation. Sleep. 2013 Nov 1;36(11):1723-35. doi: 10.5665/sleep.3138. PMID: 24179307
Harms JE, Benveniste M, Maclean JK, Partin KM, Jamieson C. Functional analysis of a novel positive allosteric modulator of AMPA receptors derived from a structure-based drug design strategy. Neuropharmacology. 2013 Jan;64:45-52. doi: 10.1016/j.neuropharm.2012.06.008. Epub 2012 Jun 23. PMID: 22735771
Young A, Machacek DW, Dhara SK, Macleish PR, Benveniste M, Dodla MC, Sturkie CD, Stice SL. Ion channels and ionotropic receptors in human embryonic stem cell derived neural progenitors. Neuroscience. 2011 Sep 29;192:793-805. doi: 10.1016/j.neuroscience.2011.04.039. Epub 2011 Jun 7. PMID: 21672611
Timm DE, Benveniste M, Weeks AM, Nisenbaum ES, Partin KM. Structural and functional analysis of two new positive allosteric modulators of GluA2 desensitization and deactivation. Mol Pharmacol. 2011 Aug;80(2):267-80. doi: 10.1124/mol.110.070243. Epub 2011 May 4. PMID: 21543522
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