Brenda L. Bloodgood
How Neuronal Computations Change in Response to an Animal’s Interactions with the Environment
From the moment an animal is born, its brain is working to extract information from the environment in order to initiate appropriate behavioral responses. This is done through the dynamic activity of excitatory and inhibitory neurons that are organized into synaptically connected circuits. My lab is working towards understanding how an animal’s experiences can change the function of individual synapses and the pattern of connectivity among neurons within a microcircuit. We approach this problem by focusing on the interplay between neuronal activity, gene regulation and synapse function in order to reveal principles that are used by the genome to modify circuits and ultimately shape behavior.
Our current research is centered on investigating how the transcription factor Npas4 alters synapse and microcircuit function. Previously I have shown that when mouse hippocampal neurons transiently express Npas4 in vivo, they undergo a significant rearrangement of inhibitory synaptic inputs, simultaneously recruiting inhibitory synapses to the soma while destabilizing those in the dendrites. We hypothesize that reorganization of inhibition in this way will limit the output of the neuron while redefining the rules of dendritic information processing and plasticity.
We use a combination of high-throughput sequencing, optogenetics, electrophysiology, and two-photon neurotransmitter uncaging to deconstruct transcriptionally driven circuit plasticity. Specifically we are addressing the following, 1) how does Npas4 translate ongoing neuronal activity into changes in inhibitory synapses? 2) Which elements of the local inhibitory microcircuit are transcriptionally regulated? And 3) how does plasticity of dendritic inhibitory synapses alter postsynaptic information processing? Through answering these questions we will identify pathways that underlie the genomic translation of neuronal activity into changes in microcircuit function and identify how disruption of these pathways can lead to disease. .