Corticofugal postsynaptic potentials and their frequency specific impact on auditory midbrain neurons

Abstract

Neuroanatomical studies reveal a great amount of descending (corticofugal) projections from the primary auditory cortex (AI) to all subcortical regions such as the central nucleus of the inferior colliculus (ICc). In the past 20 years, physiological studies have shown that the corticofugal system implements a highly frequency-specific modulation of sound information processing in the ascending auditory system. Specifically, focal electrical stimulation of the AI (ESAI) facilitates subcortical neurons when the best frequency (BF) of subcortical neurons is identical to the BF of cortical neurons (physiologically matched). In contrast, ESAI inhibits subcortical neurons when their BFs are different (unmatched). ESAI also shifts the BFs of unmatched subcortical neurons towards the BF of cortical neurons. While previous physiological findings have been achieved using extracellular recordings, to date, little is known about the cellular mechanism(s) underlying such highly, frequency-specific corticofugal modulation. An immediate question this raises is: what corticofugal postsynaptic potentials may be found in matched and unmatched subcortical neurons? A subsequent, critical question to ask is how the corticofugal postsynaptic potentials interplay with ascending (tone-evoked) postsynaptic potentials. This thesis sets out to answer these two questions by examining the corticocolliculuar (AI-to-ICc) synaptic activities in a mouse model. The membrane potential of ICc neurons was recorded by in vivo whole-cell patch current-clamp. I found that ESAI primarily evoked excitatory postsynaptic potential (EPSP) in ICc neurons. ESAI-evoked ICc EPSPs were larger in matched than in unmatched neurons. I further examined how ESAI-evoked EPSPs influence the tone-evoked EPSPs of ICc neurons. My data show that ESAI-evoked EPSPs facilitated tone-evoked EPSPs of matched neurons, but inhibited tone-evoked EPSPs of unmatched neurons. My findings reveal for the first time that corticofugal postsynaptic potentials are excitatory and frequency-dependent, and they interact with the ascending synaptic inputs in a frequency-specific manner.