Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus

Abstract

The behaviour-contingent rhythmic synchronization of neuronal activity is reported by local field potential oscillations in the theta, gamma and sharp wave-related ripple (SWR) frequency ranges. In the hippocampus, pyramidal cell assemblies representing temporal sequences are coordinated by GABAergic interneurons selectively innervating specific postsynaptic domains, and discharging phase locked to network oscillations. We compare the cellular network dynamics in the CA1 and CA3 areas recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. The axon initial segment is exclusively innervated by axo-axonic cells, preferentially firing after the peak of the pyramidal layer theta cycle, when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs, when many pyramidal cells fire synchronously. This dual inverse correlation demonstrates the key inhibitory role of axo-axonic cells. Parvalbumin-expressing basket cells fire phase locked to field gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, together with dendrite-innervating bistratified cells, phasing pyramidal cell discharge. Subcellular domain-specific GABAergic innervation probably developed for the coordination of multiple glutamatergic inputs on different parts of pyramidal cells through the temporally distinct activity of GABAergic interneurons, which differentially change their firing during different network states.

Space in the brain: how the hippocampal formation supports spatial cognition

“…Here, we note that the rich functionality conferred by oscillatory systems in the hippocampal formation requires a vast supportive network of inhibitory neurons. Somogyi et al in this issue [49] review important work on the classes of interneurons (currently numbering ca 20 in CA1) that support and control dominant hippocampal oscillations, such as theta, gamma and ripples, emphasizing the way in Figure 1. Schematic overview of major anatomical pathways in the hippocampal formation of the rat.…”

Unit Activity of Hippocampal Interneurons before Spontaneous Seizures in an Animal Model of Temporal Lobe Epilepsy

“…Blocking inhibitory synaptic transmission causes seizure activity (Schwartzkroin and Prince, 1980). In patients with temporal lobe epilepsy, GABAergic neurons (de Lanerolle et al, 1989), synapses (Brooks-Kayal et al, 1998), and circuits (Mathern et al, 1995) are aberrantly changed in the hippocampal formation, where spontaneous seizures frequently begin (Quesney, 1986;Spencer et al, 1987;Sperling and O'Connor, 1989).…”

Untangling the pathomechanisms of temporal lobe epilepsy—The promise of epileptic biomarkers and novel therapeutic approaches

“…Since adjacent GABAergic synapses can have completely opposite temporal dynamics in vivo, these terms no longer make sense without specifying the GABA-releasing cell type (Somogyi et al, 2014). Genetic labeling with fluorescent proteins of defined subsets of interneurons would allow their identification and targeting during electrophysiological recordings or imaging experiments.…”

“…They are strategically positioned to influence the output of principal cells, to regulate spike timing, oscillation rate and synchronization of their targets. Axo-axonic cells (Somogyi et al, 1983) innervate exclusively the axon initial segment, therefore they can modulate the action potential initiation. The GABAergic axon terminals of the bistratified cells (Buhl et al, 1994) are co-aligned with the glutamatergic Schaffer collateral input to the dendrites of pyramidal cells, therefore they can provide pathway-specific inhibition.…”