Vadim Bolshakov, Ph.D.

Associate Professor of Psychiatry

We utilize a combination of electrophysiological, cell biological, and molecular genetic techniques to investigate the molecular mechanism of synaptic transmission at central synapses. More recently we have begun to explore the synaptic mechanisms of learned fear using fear conditioning training paradigm. Now we are trying to relate long-term synaptic modifications at the amygdala synapses induced by behavioral training to memory of this conditioned experience. We have recently demonstrated that auditory fear conditioning, a form of fear learning, occludes electrically induced long-term potentiation (LTP) in the cortico-amygdala pathway that conveys auditory information to the lateral amygdala by way of projections from the auditory cortex. This cortico-amygdala LTP induced with electrical stimulation in slices was mechanistically similar to synaptic enhancements induced by behavioral training. These findings provide the direct causal link between LTP and fear memory. We currently continue this line of research aiming to delineate synaptic mechanisms and molecular pathways underlying learned fear.

References:

• Tsvetkov E, Carlezon WA, Benes F, Kandel E and Bolshakov VY (2002) Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic transmission in the cortical pathway to the lateral amygdala. Neuron 34, 289-300.
• Shumyatsky GP, Tsvetkov E, Malleret G, Vronskaya S, Hatton M, Hampton L, Battey JF, Dulac C, Kandel ER, and Bolshakov VY (2002) Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear. Cell 111, 905-918.
• Hinds HL, Goussakov I, Nakazawa K, Tonegawa S, Bolshakov VY (2003) Essential function of a-CaMKII in neurotransmitter release at a glutamatergic central synapse. PNAS 100, 4275-4280.
• Tsvetkov E, Shin RM, Bolshakov VY (2004) Glutamate uptake determines pathway specificity of long- term potentiation in the neural circuitry of fear conditioning. Neuron 41, 139-151.
• Shumyatsky GP, Malleret G, Shin RM, Tully K, Takizawa S, Tsvetkov E, Zakharenko SS, Joseph J, Vronskaya, Yin DQ, Schubart UK, Kandel ER, Bolshakov VY (2005) Stathmin, a gene enriched in the amygdala, controls both learned and innate fear. Cell 123.