Research Interests:

Investigation of the mechanisms by which seizures are produced in the brain, mechanisms by which the brain becomes seizure susceptible, and innovative methods for suppressing seizures.

Keywords:

Synaptic plasticity, CNS cell cultures, progenitor cells, patch clamp recordings.

Research Summary:

Dr. Marc Dichter, Professor of Neurology and Pharmacology, is actively involved in analyzing short term, frequency-dependent plasticity between hippocampal excitatory and inhibitory neurons, both in dissociated cell culture and in cultured hippocampal slices. This work focuses on both presynaptic and postsynaptic changes in synaptic function and involves patch clamp recordings from pairs of synaptically coupled neurons. As such, both elements of the synapse can be monitored and controlled while the synaptic plasticity is examined. In addition, the research examines pharmacological modulation of excitatory and inhibitory synaptic receptors and the correlation of receptor subtype with physiological actions. The lab has also been analyzing the “generic” molecular differences between excitatory neurons and inhibitory neurons in mammalian CNS, using single cell mRNA expression profiling in collaboration with Dr. Jim Eberwine. In addition, Dr. Dichter has discovered a new class of hippocampal progenitor cells that can be converted into astrocytes, oligodendocytes and neurons and the lab is investigating the mechanisms underlying the latter differentiation. Dr. Dichter's laboratory routinely cultures mammalian CNS, in either dissociated cell culture or slice culture. These preparations, allow a combination of cellular electrophysiology, pharmacology and molecular biology to be performed on the same preparation, in normal brain and in diseased animal and human brain.

Possible Lab Rotation Projects:

a. Analysis of short-term plasticity of excitatory synapses when both AMPA and NMDA components are active. This project involves patch clamp recordings from pairs of hippocampal neurons maintained in culture.

b. Cloning hippocampal progenitor cells from primary cultures

c. Analyzing factors that control the neuronal differentiation of hippocampal progenitor cells.

Key References:

1. Wilcox K, Dichter M. Paired pulse depression of inhibition in cultured hippocampal neurons is due to a presynaptic mechanism independent of GABAB autoreceptor activation, J. Neurosci, 14, 1775-1788, 1994.

2. Maki R, Cummings D, Dichter M. Frequency dependent depression of excitatory synaptic transmission does not involve activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons, J. Neurophysiol., 74:1671-1674, 1996.

3. Cao Y, Wilcox K, Martin, C, Rachinsky T, Eberwine J, Dichter M. Presence of mRNA for glutamic acid decarboxylase in both excitatory and inhibitory neurons, PNAS 93:9844-9849, 1996.

4. Wilcox K, Maki R, Dichter M. Glycine regulation of synaptic NMDA receptors in hippocampal neurons, J. Neurophysiol. 76:3415-3424, 1996.

5. Sloviter R, Dichter M, Rachinsky T, Dean E, Goodman J, Sollas AL, Martin, D. Basal

expression and induction of glutamate decarboxylase and GABA in excitatory granule cells of the rat and monkey hippocampal dentate gyrus, J. Comp. Neurol., 373:593-618, 1996.

6. Litt B, Esteller R, Echauz J, D'Allessandro M, Shor R, Henry T, Pennell P, Epstein C, Bakay R, Dichter M, Vachtsevanos G. Epileptic seizures may begin hours in advance of clinical onset: a report of five patients, Neuron, 30:51-64, 2001.

7. Aaron G, Dichter M. Excitatory synapses from CA3 pyramidal cells onto neighboring pyramidal cells differ from those onto inhibitory interneurons, Synapse, in press.