Brain function is tightly controlled by a delicate balance of excitation (E) and inhibition (I) that is dynamically maintained in single neurons and within neural networks. An imbalance of E/I is implicated in many neuropathological and psychiatric disorders. Research in my laboratory aims to understand how E/I balance is achieved in a neural landscape that is ever-changing. For example, glutamatergic synapses that mediate excitation readily modify their strength and number during learning and memory. Consequently, GABAergic synapses that mediate inhibition should also be plastic, exhibiting changes that match their excitatory counterpart. Notably, little is known about the reciprocal interactions between excitatory and inhibitory synaptic signaling. This is due to the fact that GABAergic synapses arise from a heterogeneous population of interneurons and occur on discrete sub-cellular postsynaptic compartments. With the advent of advanced optical, pharmacological and genetic tools, we can now dissect the richness of GABAergic interneurons that mediate disparate forms of synaptic inhibition. To monitor and stimulate individual synapses, we will combine electrophysiology and optogenetics with calcium imaging and GABA/glutamate uncaging using a state-of-the-art 2-photon microscope system to study the cellular and molecular mechanisms by which excitatory and inhibitory synapses mutually regulate each other.

Specific goals are to determine:

1. How individual GABAergic synapses regulate excitatory synaptic signaling and dendritic spine plasticity
2. How specific GABAergic interneuron types contribute to cortical processing at the systems level to modulate behavior.
3. How disparate forms of synaptic inhibition are regulated to match changes in excitatory neurotransmission.
4. How sensory experience modifies inhibitory circuits during development.

• Chiu CQ, Martenson JS, Yamazaki M, Natsume R, Sakimura K, Tomita S, Tavalin SJ, Higley MJ. Input-specific NMDAR-dependent potentiation of dendritic GABAergic inhibition. Neuron 97, 368-377, 2018.
• Amatrudo J, Olson JP, Lur G, Chiu CQ, Higley MJ, Ellis-Davies GC. Wavelength-selective one- and two-photon uncaging of GABA. ACS Chem. Neurosci. 5, 64-70, 2014.
• Chiu CQ*, Lur G*, Morse TM, Carnevale NT, Ellis-Davies GC, Higley MJ. Compartmentalization of GABAergic inhibition by dendritic spines. Science 340, 759-762, 2013. *equal contribution
• Chávez AE, Chiu CQ, Castillo PE. TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nature Neurosci. 13, 1511-1518, 2010.
• Chiu CQ, Puente N, Grandes P, Castillo PE. Dopaminergic modulation of endocannabinoid-mediated plasticity at GABAergic synapses in the prefrontal cortex. J. Neurosci. 30, 7236-7248, 2010.