TNF-α Orchestrates Experience-Dependent Balancing of Excitation-Inhibition in the Olfactory Cortex

Project: Research

Project Details

Description

Precise regulation of excitation and inhibition (E-I) is crucial for cortical processing of sensory information. The anterior piriform cortex (APC) is instrumental to odor perception and learning as it processes odor properties at just one synapse downstream of the olfactory bulb (OB). Our previous results showed that deprivation of odor experience produces target-specific modulation of inhibitory transmission: naris occlusion (NO) selectively altered inhibitory transmission in superficial pyramidal (SP), but not semilunar (SL), principal neurons. However, it is unclear how odor experience modulates excitatory and inhibitory circuit properties in the APC. Here we obtained preliminary data that uncovered a new form of homeostatic plasticity: NO enhanced both EPSC and IPSC amplitude selectively in SP cells, but, ultimately, E-I ratio was maintained. What could be a molecular mechanism that regulates this form of E-I homeostatic balance in APC? Signaling molecules like retinoic acid and TNF-α have been shown to be instrumental in orchestrating plasticity in auditory and visual cortices. However, whether they play a role in olfactory cortical plasticity has not been explored. Here we propose that TNF-α orchestrates the balance of E-I in APC in an activitydependent manner. I will use a combination of slice electrophysiology, optogenetics, mouse genetics, and immunofluorescent staining to probe the role of TNF-α on regulating excitation and inhibition of SL and SP neural activity. Objective 1 will determine how NO alters recurrent excitation and inhibition in APC principal neurons. Objective 2 will examine how NO regulates excitatory and inhibitory synaptic proteins in APC. Objective 3 will examine how TNF-α regulates the structural and physiological changes induced by NO. Elucidating the molecular mechanism of experience-dependent plasticity in the olfactory cortex will provide a new theoretical framework for homeostatic and target-specific modulation of E-I balance.
Project number9043125
Grant typeGRF
StatusActive
Effective start/end date1/09/21 → …

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