Behavior-dependent specialization of identified hippocampal interneurons

Abstract

A large variety of GABAergic interneurons control information processing in hippocampal circuits governing the formation of neuronal representations. Whether distinct hippocampal interneuron types contribute differentially to information-processing during behavior is not known. We employed a novel technique for recording and labeling interneurons and pyramidal cells in drug-free, freely-moving rats. Recorded parvalbumin-expressing basket interneurons innervate somata and proximal pyramidal cell dendrites, whereas nitric-oxide-synthase-and neuropeptide-Y-expressing ivy cells provide synaptic and extrasynaptic dendritic modulation. Basket and ivy cells showed distinct spike timing dynamics, firing at different rates and times during theta and ripple oscillations. Basket but not ivy cells changed their firing rates during movement, sleep and quiet wakefulness, suggesting that basket cells coordinate cell assemblies in a behavioral state-contingent manner, whereas persistently-firing ivy cells might control network excitability and homeostasis. Different interneuron types provide GABA to specific subcellular domains at defined times and rates, thus differentially controlling network activity during behavior.GABAergic interneurons control information processing in cortical circuits as percussionists set the rhythm for a melody, or traffic lights regulate the movement of cars through a city. Interneurons generate oscillatory activity 1, 2 , synchronize the activity of pyramidal cells 3 and set time windows for synaptic integration 4 . A large diversity of interneuronal types is a hallmark of cortical circuits. 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. In the barrel cortex of head-restrained mice, groups of interneurons with distinct membrane dynamics during different behavioral states have been described 16,17 and in the hippocampus unidentified interneurons or interneurons belonging to heterogeneous groups expressing parvalbumin and/or somatostatin have been reported [18][19][20][21] to fire with different firing patterns during network oscillations. But, how do specific types of identified interneurons control the activity of cortical circuits in freely-moving animals? CouldCorrespondence and requests for materials should be addressed to D.L. (damien.lapray@pharm.ox.ac.uk) Results Identification of neurons recorded in freely-moving ratsWe recorded the activity of parvalbumin (PV)-expressing basket, ivy and pyramidal cells in the dorsal CA...

Fast-spiking, parvalbumin + GABAergic interneurons: From cellular design to microcircuit function

“…The activity of PV + interneurons in the hippocampus substantially changes during network oscillations, such as theta (4-10 Hz), gamma (40-100 Hz), and ripple activity (140-200 Hz). In the absence of oscillatory activity, action potential frequency is low (6.5 Hz;87). During theta oscillations, action potential frequency markedly increases (21 Hz).…”

Generation of physiological and pathological high frequency oscillations: the role of perisomatic inhibition in sharp-wave ripple and interictal spike generation

“…Periodic perisomatic inhibition has been held responsible for the generation of the high-frequency components and the phaselocking of neuronal activity [3], but no convincing data are available about the initiation of SWRs, although the SWR state is considered an "off-line" state of the hippocampus [1 2]. To uncover the participation of different types of neurons in SWR generation, several in vivo [28][29][30][31][32][33][34] and in vitro [35][36][37] studies have examined the firing characteristics of identified neuron types (summarized in [38]). Mostly similar relative firing patterns were found for the examined cell types, but there were some contradictory results, which might have arisen from differences between the CA1 and the CA3 area, and most importantly from anaesthetized compared to freely moving animals or in vitro slices.…”

Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus

“…While it is clear that basket cells inhibit their target neurons, the effect of axo-axonic cells is still debated and it can be either excitatory (Szabadics et al, 2006) or inhibitory (Glickfeld et al, 2009). In addition, the three perisomatic interneuron groups are active at different times and show different firing patterns during network oscillations in vivo (Klausberger et al, 2003;Klausberger et al, 2005;Tukker et al, 2007;Lasztóczi et al, 2011;Lapray et al, 2012;Tukker et al, 2013) and also in in vitro preparations Hájos et al, 2013).…”