The many tunes of perisomatic targeting interneurons in the hippocampal network

Abstract

The axonal targets of perisomatic targeting interneurons make them ideally suited to synchronize excitatory neurons. As such they have been implicated in rhythm generation of network activity in many brain regions including the hippocampus. However, several recent publications indicate that their roles extend beyond that of rhythm generation. Firstly, it has been shown that, in addition to rhythm generation, GABAergic perisomatic inhibition also serves as a current generator contributing significantly to hippocampal oscillatory EEG signals. Furthermore, GABAergic interneurons have a previously unrecognized role in the initiation of hippocampal population bursts, both in the developing and adult hippocampus. In this review, we describe these new observations in detail and discuss the implications they have for our understanding of the mechanisms underlying physiological and pathological hippocampal network activities. This review is part of the Frontiers in Cellular Neuroscience's special topic entitled "GABA signaling in health and disease" based on the meeting at the CNCR Amsterdam.

Keywords: GABA; gamma oscillation; hippocampus; inhibition; network oscillation; perisomatic targeting interneuron; population burst; sharp wave-ripple.

Figure 1

Schematic diagram of hippocampal local field potentials and the underlying current sinks and sources. (A) Recording electrodes placed in the dendritic and somatic regions of the hippocampus show a phase reversal for both evoked responses and oscillatory activity. (B) Excitatory synaptic events at the apical dendrite of pyramidal neurons generate an active current sink as positive ions flow into neurons; a concurrent passive source is recorded from the somatic region. (C) Inhibitory synaptic events at the perisomatic regions of pyramidal neurons generate an active source accompanied by a passive current sink at the dendrites.

Figure 2

Schematic diagram of network activity underlying hippocampal population bursts. (A) Spontaneous network synchronizations as seen in the immature hippocampus are thought to be generated by the excitatory action of GABAergic neurons, which depolarize and recruit a population of pyramidal neurons into a population burst. (B) Sharp wave-ripple population bursts as seen in the adult hippocampus may be initiated by the activity of an inhibitory interneuron temporarily silencing a subset of pyramidal neurons followed by rebound excitation, recruiting a larger population of pyramidal neurons into a population burst.