Cholinergic control of sensory synaptic transmission in primary and nonprimary auditory thalamus of rat.

Abstract

A large body of literature now indicates that behavior-dependent functional adaptations in the central auditory system are in large part regulated by a cholinergic modulatory input from the midbrain reticular formation. The central hypothesis behind this thesis is that acetylcholine is capable of modulating auditory synaptic transmission in a synaptic pathway-specific manner. The auditory thalamocortical system consists of primary (lemniscal) and nonprimary (nonlemniscal) auditory thalamocortical projections that originate from two segregated cell populations located in the ventral (MGv) and dorsal (MGd) divisions of the medial geniculate body (MGB). The two pathways are known to engage in different aspects of auditory function. A thalamic explant preparation was employed for the study, in which the parallel MGB pathways, together with their sensory afferents, can be maintained and accessed in vitro for comparative electrophysiological studies. The following summarizes the main findings described in this thesis. 1. When the MGB explant is persistently exposed to acetylcholine, the evoked sensory synaptic responses from MGv neurons consist almost exclusively of a single action potential and are able to follow high-frequency stimuli. In contrast, nonprimary or MGd neurons responded to sensory pathway stimulation with a stereotyped burst of action potentials which failed to follow a stimulation frequency higher than 5 Hz. 2. Intracellular recordings revealed that muscarine induces a slow membrane depolarization in ventral neurons, which helps EPSPs trigger single action potentials but prevents them from eliciting low threshold Ca2+ spike (LTS)-burst complexes. An opposite, membrane hyperpolarization response was observed in dorsal cells where muscarinic receptor activation promotes coupling between the EPSP and the LTS-burst. 3. Muscarine blocks a leak and a Ca2+-dependent K+ membrane conductance K(ca) in ventral MGB neurons whereas in dorsal cells it opens leak K+ channels and largely has no effect on K(ca). It is concluded that a differential modulatory mechanism mediated by muscarinic receptor activation helps create and maintain a fast synaptic responding mode in the primary thalamocortical pathway for high-fidelity sensory relay and a slower but robust bursting transmittal mechanism in the nonprimary pathway suitable for detection of sensory events and induction of long term synaptic plasticity in target cells.