| Gleb Shumyatsky
Assistant Professor
Rutgers University
Dept. of Genetics
Life Sciences Building. Room 322
145 Bevier Road
Piscataway. NJ 08854
Office (732) 445 - 1223
Lab (732) 445-1027, ext. 40087
FAX - 1147
gleb@biology.rutgers.edu
Visit the Shumyatsky Lab! |
Molecular and cellular
mechanisms of learning and memory
We are studying molecular and cellular
mechanisms of learning and memory focusing on learned fear. which is the
most simple and evolutionally conserved type of memory in mammals. The main area of the brain that plays a
critical role in forming memories of fearful experiences is the amygdala. The neural circuitry of learned fear is well characterized at the
anatomical and behavioral levels. which
makes learned fear particularly
attractive as a model to delineate molecular mechanisms of memory. However. genes and biochemical pathways determining unique characteristics
of fear are largely unknown.
To study learned fear at the molecular level. we screened for amygdala-enriched genes. As a result. we have identified some
of the genetic components of a specific inhibitory neural circuitry in the brain
that plays an important role in how fear is regulated and experienced. Specifically. we have found a gene called gastrin-releasing peptide (Grp)
that was highly enriched in the amygdala. The Grp gene encodes a
neurotransmitter called gastrin-releasing peptide (GRP). Using a combination of
mouse genetics. electrophysiology and behavioral approaches. we have found that
GRP plays an important role in regulating the fear response. In fear
conditioning experiments compared to normal mice. mice that had a deletion of
the gene encoding the receptor for GRP displayed increased fear. The knock-out
mice also showed an enhancement in the learning-related cellular process. long-term potentiation (LTP). Therefore. the missing GRPR gene was linked to
dysfunction in regulating memory of fear. Principal cells express GRP and
inhibitory interneurons express GRPR. Together they act as a mechanism
providing a unique negative feedback from interneurons to principal cells in the
amygdala. These experiments provide evidence of causal relationship between
changes in gene expression and LTP in the amygdala on one hand and changes in
learned fear on another.
Using these and similar approaches. we are
studying the roles of other amygdala-enriched genes. that we have found. in
learned fear. We are also developing a mouse with amygdala-restricted genetic
modifications. The combination of the amygdala-restricted expression with the
regulation of transgene expression using tetracycline-dependent transcription
and Cre-recombinase-based knock-out will allow for specific genetic
manipulations in a spatial and temporal manner.
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