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...

Hippocampal sharp waves are population discharges initiated by an unknown mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate action potential generation through GABAergic synapses on the axon initial segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving rats stopped firing during sharp waves, when pyramidal cells fire most. AACs fired strongly and rhythmically around the peak of theta oscillations, when pyramidal cells fire at low probability. Distinguishing AACs from other parvalbumin-expressing interneurons by their lack of detectable SATB1 transcription factor immunoreactivity, we discovered a somatic GABAergic input originating from the medial septum that preferentially targets AACs. We recorded septo-hippocampal GABAergic cells that were activated during hippocampal sharp waves and projected to CA3. We hypothesize that inhibition of AACs, and the resulting subcellular redistribution of inhibition from the axon initial segment to other pyramidal cell domains, is a necessary condition for the emergence of sharp waves promoting memory consolidation.During slow wave sleep (SWS), quiet wakefulness and consummatory behavior, largeamplitude, 30-120-ms-duration 'sharp wave' voltage deflections have been observed in extracellular recordings throughout the mammalian hippocampal formation 1 , which occur simultaneously with 130-230 Hz 'ripples' most pronounced in stratum pyramidale (sPyr) of CA1 (refs. 2,3). These sharp wave-ripple complexes (SWRs) are required for memory © 2013 Nature America, Inc. All rights reserved.Reprints and permissions information is available online at http://www.nature.com/reprints/index.html.Correspondence should be addressed to T.J.V. (tim.viney@pharm.ox.ac.uk), B.L. (balint.lasztoczi@meduniwien.ac.at) or P.S. (peter.somogyi@pharm.ox.ac.uk). AUTHOR CONTRIBUTIONS T.J.V., B.L., L.K., M.G.C., J.J.T., T.K. and P.S. collected and analyzed data and wrote the paper. To expand on the equalcontributions footnote, each of the first four authors made important-though different-contributions, and hence they should be considered equal first authors.Note: Any Supplementary Information and Source Data files are available in the online version of the paper. COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests. Europe PMC Funders GroupAuthor Manuscript Nat Neurosci. Author manuscript; available in PMC 2015 June 18. Published in final edited form as:Nat Neurosci. 2013 December ; 16(12): 1802-1811. doi:10.1038/nn.3550. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts consolidation 4 and have been postulated to originate from groups of pyramidal neurons in CA3 participating in a synchronous 'population burst', which is transmitted to the downstream CA1 region via Schaffer collaterals 5 . A proposed mechanism for SWR initiation is through disinhibition of pyramidal cells via dynamic state-dependent interactions between GABAergic neurons and glutamatergic inputs 1 . Indeed, in vivo recordings show ...

SummaryNeuropeptides acting on pre- and postsynaptic receptors are coreleased with GABA by interneurons including bistratified and O-LM cells, both expressing somatostatin but innervating segregated dendritic domains of pyramidal cells. Neuropeptide release requires high-frequency action potentials, but the firing patterns of most peptide/GABA-releasing interneurons during behavior are unknown. We show that behavioral and network states differentiate the activities of bistratified and O-LM cells in freely moving rats. Bistratified cells fire at higher rates during sleep than O-LM cells and, unlike O-LM cells, strongly increase spiking during sharp wave-associated ripples (SWRs). In contrast, O-LM interneurons decrease firing during sleep relative to awake states and are mostly inhibited during SWRs. During movement, both cell types fire cooperatively at the troughs of theta oscillations but with different frequencies. Somatostatin and GABA are differentially released to distinct dendritic zones of CA1 pyramidal cells during sleep and wakefulness to coordinate segregated glutamatergic inputs from entorhinal cortex and CA3.