Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo

Abstract

Neural-network oscillations at distinct frequencies have been implicated in the encoding, consolidation and retrieval of information in the hippocampus. Some GABA (gamma-aminobutyric acid)-containing interneurons fire phase-locked to theta oscillations (4-8 Hz) or to sharp-wave-associated ripple oscillations (120-200 Hz), which represent different behavioural states. Interneurons also entrain pyramidal cells in vitro. The large diversity of interneurons poses the question of whether they have specific roles in shaping distinct network activities in vivo. Here we report that three distinct interneuron types--basket, axo-axonic and oriens-lacunosum-moleculare cells--visualized and defined by synaptic connectivity as well as by neurochemical markers, contribute differentially to theta and ripple oscillations in anaesthetized rats. The firing patterns of individual cells of the same class are remarkably stereotyped and provide unique signatures for each class. We conclude that the diversity of interneurons, innervating distinct domains of pyramidal cells, emerged to coordinate the activity of pyramidal cells in a temporally distinct and brain-state-dependent manner.

Behavior-dependent specialization of identified hippocampal interneurons

“…Notably, PV-expressing basket or ivy cells reported here have similar spike timing relative to theta oscillations compared to those recorded under anesthesia 15,25 . This is remarkable considering that the frequency of theta oscillations is twice as high in drug-free compared to anesthetized preparations, and the average firing rates of the neurons are higher in the absence of anesthesia.…”

“…We observed that pyramidal cells fire, on average, with similar rates during different behavioral states and they are under constant control via the volume transmission 44 by GABA, NPY and nitric oxide from the dense axonal web of ivy cells. In addition, we observed that ivy cells fire with higher rates when field theta oscillations become faster in frequency and larger in amplitude reflecting increased network activity and synchrony.Notably, PV-expressing basket or ivy cells reported here have similar spike timing relative to theta oscillations compared to those recorded under anesthesia 15,25 . This is remarkable considering that the frequency of theta oscillations is twice as high in drug-free compared to anesthetized preparations, and the average firing rates of the neurons are higher in the absence of anesthesia.…”

“…Our results show that two distinct types of GABAergic interneuron, PV-expressing basket and ivy cells, the two most numerous GABAergic cell types in the hippocampal pyramidal layer, contribute differentially to behavioral state-dependent neuronal activities and 2,13,15,35,36 through their highly precise inhibitory control of pyramidal cell output 5, 37-39 . They have been predicted to provide a clock-like temporal frame for information coding by pyramidal cells 40 .…”

“…So far, an unequivocal recognition of PVexpressing basket cells is only possible by verifying both their molecular expression and axonal arborizations, because PV is expressed also by hippocampal axo-axonic, bistratifed, O-LM and some long-range projection neurons and because other types of basket cell exist which do not express parvalbumin 34 . Parvalbumin-expressing basket cells are thought to contribute to the generation of network oscillations 2,13,15,35,36 through their highly precise inhibitory control of pyramidal cell output 5, 37-39 . They have been predicted to provide a clock-like temporal frame for information coding by pyramidal cells 40 .…”

“…Different domains of pyramidal cells, such as the soma, axoninitial-segment, proximal or distal dendrites 5 are innervated by distinct types of GABAergic interneuron. They also have distinct inputs and membrane properties 6-10 and show different firing patterns during network oscillations induced in vitro [11][12][13][14] or recorded in anesthetized animals 15 , indicating distinct roles for specific interneuron types. However, research on interneurons in drug-free animals that can freely change their behavior, has so far been limited to recordings from unidentified interneurons because of technical limitations.…”