Synaptic interactions and inhibitory regulation in auditory cortex

Abstract

This Special Issue focuses on the auditory-evoked mismatch negativity (MMN), an electrophysiological index of change, and its reduction in schizophrenia. The following brief review is an attempt to complement the behavioral and clinical contributions to the Special Issue by providing basic information on synaptic interactions and processing in auditory cortex. A key observation in previous studies is that the MMN involves activation of cortical N-methyl-D-aspartate (NMDA) receptors. Yet, NMDA receptor activation is regulated by a number of synaptic events, which also may contribute to the MMN reduction in schizophrenia. Accordingly, this review will focus on synaptic interactions, notably inhibitory regulation of NMDA receptor-mediated activity, in auditory cortex.

Keywords: Auditory cortex; GABA; Glutamate; Mismatch negativity; NMDA; Neuromodulation; Nicotinic acetylcholine receptor; Synaptic integration; Thalamocortical.

Figure 1

The stereotypic synaptic response in auditory cortex evoked by afferent stimulation in vitro comprises a glutamatergic EPSP and two GABAergic IPSPs. A: the neuron is hyperpolarized or depolarized from rest via current from the patch pipette (current record under first set of traces; triangle above current record indicates time of electrical stimulus). B: shows the amplitude of each response component vs. membrane potential, and the inset shows neuron’s input resistance. C,D: Reduction of late-IPSP with the GABA-B antagonist 2-OH saclofen reveals late-EPSP (arrow in C) that is reduced by NMDA receptor antagonist APV (D). Scales in C apply to all traces. From (Metherate & Ashe, 1994).

Figure 2

Facilitation of NMDA receptor-mediated late-EPSP by paired pulse electrical stimulation, in vitro. S1 is first stimulus, S2 is second stimulus delivered at various interpulse intervals after the first. Traces (A) are from two different neurons exhibiting different resting membrane potentials, with 4–5 trials overlaid. Arrows point to optimally enhanced late-EPSP for each neuron. (B) Group data showing amplitude of enhanced late-EPSP at various interpulse intervals. From (Metherate & Ashe, 1994)

Figure 3

Afferent stimulation that activates the NMDA receptor-mediated EPSP can trigger high-frequency (gamma) cortical activity in the auditory thalamocortical slice. Top trace is local field potential, bottom trace is simultaneous intracellular recording within the same cortical “column.” Traces in (B) are enlarged from the box in (A) and show correspondence between extracellular gamma-range oscillations and intracellular membrane potential fluctuations. In particular, extracellular negative potentials tend to correspond to intracellular depolarizations (vertical dotted lines), suggesting that both reflect fast EPSPs; similarly, intervening extracellular positivities and intracellular hyperpolarizations may reflect fast IPSPs. From (Metherate & Cruikshank, 1999).