Understanding fear mechanisms in the brain can improve our strategies for treating post-traumatic stress disorder, anxiety disorders and other potentially debilitating mental illnesses that affect many people. How innate and learned fear manifest themselves in the brain and interact at the level of individual brain cells and circuits can be probed in animal models.

The Bolshakov lab focuses on cellular and molecular mechanisms of learned and innate behaviors using a combination of electrophysiological, cell biological, and optogenetic techniques. Specifically, we explore synaptic mechanisms of learned and innate fear, in an attempt to relate long-term synaptic modifications at synapses in the amygdala induced by fear conditioning to memories of this conditioned experience.

The Bolshakov laboratory has identified several mechanisms of pathway specificity of lasting synaptic modifications in fear conditioning circuits helping to maintain functional independence of the convergent inputs. These mechanisms contribute to directionality of the information flow in fear conditioning pathways, providing a mechanism for the conditioned stimulus discrimination during fear memory retrieval. The laboratory demonstrated also that both synaptic modifications in afferent inputs to the amygdala associated with fear conditioning and the ability to acquire and retain fear memory can be regulated by the neural circuitry-specific gene expression, providing genetic evidence that plasticity in the conditioned stimulus pathways serves as a cellular mechanism of fear memory formation. Recently, using optogenetic techniques, the laboratory showed that interactions between mPFC and amygdala serve an essential function in extinction of conditioned fear memory.

Currently, in collaboration with others at McLean, we are in the midst of a large study of how prenatal and early postnatal immune activation may regulate core behavioral signs associated with autism spectrum disorder (ASD) through the changes in a signal flow between different structural components of behavior driving neural circuits.