Oriens-lacunosum Moleculare Interneurons Research Articles

Understanding OLM interneurons: Characterization, circuitry, and significance in memory and navigation

Understanding the intricate mechanisms underlying memory formation and retention relies on unraveling how the hippocampus, a structure fundamental for memory acquisition, is organized. Within the complex hippocampal network, interneurons play a crucial role in orchestrating memory processes. Among these interneurons, Oriens-Lacunosum Moleculare (OLM) cells emerge as key regulators, governing the flow of information to CA1 pyramidal cells. In this review, we explore OLM interneurons in detail, describing their mechanisms and effects on memory processing, particularly in spatial and contextual memory tasks. Our aim is to provide a detailed understanding of how OLM interneurons contribute to the dynamic landscape of memory formation and retrieval.

Functional specialization of hippocampal somatostatin-expressing interneurons

Hippocampal somatostatin-expressing (Sst) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive Sst-IN subpopulations census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of Sst-INs based on transcriptomic features. Four mouse models based on single or combinatorial Cre- and Flp- expression differentiated functionally distinct subpopulations of CA1 hippocampal Sst-INs that largely tiled the morpho-functional parameter space of the Sst-INs superfamily. Notably, the Sst;;Tac1 intersection revealed a population of bistratified INs that preferentially synapsed onto fast-spiking interneurons (FS-INs) and were sufficient to interrupt their firing. In contrast, the Ndnf;;Nkx2-1 intersection identified a population of oriens lacunosum-moleculare INs that predominantly targeted CA1 pyramidal neurons, avoiding FS-INs. Overall, our results provide a framework to translate neuronal transcriptomic identity into discrete functional subtypes that capture the diverse specializations of hippocampal Sst-INs.

Hippocampal Interneuronal α7 nAChRs Modulate Theta Oscillations in Freely Moving Mice

Muscarinic acetylcholine receptors (mAChRs) are critically involved in hippocampal theta generation, but much less is known about the role of nicotinic AChRs (nAChRs). Here we provide evidence that α7 nAChRs expressed on interneurons, particularly those in oriens lacunosum moleculare (OLM), also regulate hippocampal theta generation. Local hippocampal infusion of a selective α7 nAChR antagonist significantly reduces hippocampal theta power and impairs Y-maze spontaneous alternation performance in freely moving mice. By knocking out receptors in different neuronal subpopulations, we find that α7 nAChRs expressed in OLM interneurons regulate theta generation. Our invitro slice studies indicate that α7 nAChR activation increases OLM neuron activity that, in turn, enhances pyramidal cell excitatory postsynaptic currents (EPSCs). Our study also suggests that mAChR activation promotes transient theta generation, while α7 nAChR activation facilitates future theta generation by similar stimulations, revealing a complex mechanism whereby cholinergic signaling modulates different aspects of hippocampal theta oscillations through different receptor subtypes.

Synergy of Glutamatergic and Cholinergic Modulation Induces Plateau Potentials in Hippocampal OLM Interneurons.

Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that are implicated in the regulation of information flow in the CA1 circuit, inhibiting cortical inputs to distal pyramidal cell dendrites, whilst disinhibiting CA3 inputs to pyramidal cells. OLM cells express metabotropic cholinergic (mAChR) and glutamatergic (mGluR) receptors, so modulation of these cells via these receptors may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify OLM cells, we found that both mAChR and mGluR activation caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both mAChR- and mGluR-induced plateau potentials were eliminated by blocking transient receptor potential (TRP) channels, and were dependent on intracellular calcium concentration and calcium entry. Pharmacological tests indicated that Group I mGluRs are responsible for the glutamatergic induction of plateaus. There was also a pronounced synergy between the cholinergic and glutamatergic modulation, plateau potentials being generated by agonists applied together at concentrations too low to elicit any change when applied individually. This synergy could enable OLM cells to function as coincidence detectors of different neuromodulatory systems, leading to their enhanced and prolonged activation and a functional change in information flow within the hippocampus.

Altered Dynamics of Canonical Feedback Inhibition Predicts Increased Burst Transmission in Chronic Epilepsy.

Inhibitory interneurons, organized into canonical feedforward and feedback motifs, play a key role in controlling normal and pathological neuronal activity. We demonstrate prominent quantitative changes in the dynamics of feedback inhibition in a rat model of chronic epilepsy (male Wistar rats). Systematic interneuron recordings revealed a large decrease in intrinsic excitability of basket cells and oriens-lacunosum moleculare interneurons in epileptic animals. Additionally, the temporal dynamics of interneuron recruitment by recurrent feedback excitation were strongly altered, resulting in a profound loss of initial feedback inhibition during synchronous CA1 pyramidal activity. Biophysically constrained models of the complete feedback circuit motifs of normal and epileptic animals revealed that, as a consequence of altered feedback inhibition, burst activity arising in CA3 is more strongly converted to a CA1 output. This suggests that altered dynamics of feedback inhibition promote the transmission of epileptiform bursts to hippocampal projection areas.SIGNIFICANCE STATEMENT We quantitatively characterized changes of the CA1 feedback inhibitory circuit in a model of chronic temporal lobe epilepsy. This study shows, for the first time, that dynamic recruitment of inhibition in feedback circuits is altered and establishes the cellular mechanisms for this change. Computational modeling revealed that the observed changes are likely to systematically alter CA1 input-output properties leading to (1) increased seizure propagation through CA1 and (2) altered computation of synchronous CA3 input.

Single-cell RNA-Seq characterization of anatomically identified OLM interneurons in different transgenic mouse lines.

Inhibitory GABAergic interneurons create different brain activity patterns that correlate with behavioural states. In this characterizing study, we used single‐cell RNA‐Seq to analyse anatomically‐ and electrophysiologically identified hippocampal oriens‐lacunosum moleculare (OLM) interneurons. OLMs express somatostatin (Sst), generate feedback inhibition and play important roles in theta oscillations and fear encoding. Although an anatomically‐ and biophysically homogenous population, OLMs presumably comprise of two functionally distinct types with different developmental origins, inferred from the expression pattern of serotonin type‐3a (5‐HT3a, or Htr3a) receptor subunit and 5‐HT excitability in a set of OLMs. To broadly characterize OLM cells, we used the Sst‐Cre and the BAC transgenic Htr3a‐Cre mouse lines and separately analysed SstCre‐OLM and Htr3aCre‐OLM types. We found a surprisingly consistent expression of Npy in OLMs, which was previously not associated with the identity of this type. Our analyses furthermore revealed uniform expression of developmental origin‐related genes, including transcription factors and neurexin isoforms, without providing support for the current view that OLMs may originate from multiple neurogenic zones. Together, we found that OLMs constitute a highly homogenous transcriptomic population. Finally, our results revealed surprisingly infrequent expression of Htr3a in only ~10% of OLMs and an apparently specific expression of the 5‐HT3b subunit‐coding gene Htr3b in Htr3aCre‐OLMs, but not in SstCre‐OLMs. However, additional in situ hybridization experiments suggested that the differential expression of Htr3b may represent an unexpected consequence arising from the design of the Htr3a‐Cre BAC transgenic line.

Electrophysiological and Morphological Characterization of Chrna2 Cells in the Subiculum and CA1 of the Hippocampus: An Optogenetic Investigation.

The nicotinic acetylcholine receptor alpha2 subunit (Chrna2) is a specific marker for oriens lacunosum-moleculare (OLM) interneurons in the dorsal CA1 region of the hippocampus. It was recently shown using a Chrna2-cre mice line that OLM interneurons can modulate entorhinal cortex and CA3 inputs and may therefore have an important role in gating, encoding, and recall of memory. In this study, we have used a combination of electrophysiology and optogenetics using Chrna2-cre mice to determine the role of Chrna2 interneurons in the subiculum area, the main output region of the hippocampus. We aimed to assess the similarities between Chrna2 subiculum and CA1 neurons in terms of the expression of interneuron markers, their membrane properties, and their inhibitory input to pyramidal neurons. We found that subiculum and CA1 dorsal Chrna2 cells similarly expressed the marker somatostatin and had comparable membrane and firing properties. The somas of Chrna2 cells in both regions were found in the deepest layer with axons projecting superficially. However, subiculum Chrna2 cells displayed more extensive projections with dendrites which occupied a significantly larger area than in CA1. The post-synaptic responses elicited by Chrna2 cells in pyramidal cells of both regions revealed comparable inhibitory responses elicited by GABAA receptors and, interestingly, GABAB receptor mediated components. This study provides the first in-depth characterization of Chrna2 cells in the subiculum, and suggests that subiculum and CA1 Chrna2 cells are generally similar and may play comparable roles in both sub-regions.

Septal cholinergic neurons gate hippocampal output to entorhinal cortex via oriens lacunosum moleculare interneurons

Neuromodulation of neural networks, whereby a selected circuit is regulated by a particular modulator, plays a critical role in learning and memory. Among neuromodulators, acetylcholine (ACh) plays a critical role in hippocampus-dependent memory and has been shown to modulate neuronal circuits in the hippocampus. However, it has remained unknown how ACh modulates hippocampal output. Here, using in vitro and in vivo approaches, we show that ACh, by activating oriens lacunosum moleculare (OLM) interneurons and therefore augmenting the negative-feedback regulation to the CA1 pyramidal neurons, suppresses the circuit from the hippocampal area CA1 to the deep-layer entorhinal cortex (EC). We also demonstrate, using mouse behavior studies, that the ablation of OLM interneurons specifically impairs hippocampus-dependent but not hippocampus-independent learning. These data suggest that ACh plays an important role in regulating hippocampal output to the EC by activating OLM interneurons, which is critical for the formation of hippocampus-dependent memory.

Novel markers for OLM interneurons in the hippocampus.

Oriens-lacunosum moleculare (OLM) cells are a major subclass of hippocampal interneurons involved in controlling synaptic plasticity in Shaffer collateral synapses (Leao et al., 2012) and electrogenesis in pyramidal cell (PC) dendrites (Lovett-Barron et al., 2012). Their firing phase is locked with theta oscillations, which imply a role for these cells in theta rhythmogenesis (Klausberger and Somogyi, 2008; Forro et al., 2015). OLM interneurons also appear to be key in the pathophysiology of epilepsy (Dugladze et al., 2007) and is the most vulnerable interneuron population in models of epilepsy (Dinocourt et al., 2003).

Network models provide insight into how oriens-lacunosum-moleculare (OLM) and bistratified cell (BSC) interactions influence local CA1 theta rhythms

Although hippocampal theta, a 4-12 Hz rhythm associated with episodic memory, has been studied extensively, the cellular mechanisms underlying its generation are unclear. OLM cells have been considered pacemakers of local CA1 theta [1], but recent experimental work has disputed this role [2]. The complex interactions that OLM cells have with other cell types, such as bistratified cells (BSCs) [3], make their contribution to network rhythms difficult to determine experimentally. One can address this issue using mathematical network models, which allow one to explore the contribution of specific cell populations and network connectivity in a simplified setting, and make predictions to guide further experimental work. Thus, we created a network model that is tied to experimental work on both the cellular and network level, and explored how cell interactions affect the power of local oscillations. We derived cellular properties from patch clamp recordings of fast-spiking parvalbumin-positive (PV+) interneurons – likely comprising basket cells (BCs), axo-axonic cells (AACs), and BSCs – and of somatostatin-positive putative OLM cells in the CA1 region of an intact hippocampus in vitro, and used these properties to constrain Izhikevich-type models of BCs/AACs, BSCs, and OLM interneurons. We constructed our network model with these individual cell models, and constrained network size, connectivity, and synaptic properties with experimental data. Experimental excitatory postsynaptic currents (EPSCs) recorded during endogenous CA1 theta oscillations were used to drive the various cell model populations, and we used a simple local field potential (LFP) model to integrate the effects of cell firing. To determine how the interactions between OLM cells and BSCs affect local theta rhythms, we explored how specific features of the network affected model LFP power. In addition, we simulated optogenetic experiments by silencing the OLM cell model population during the network rhythm. Spike characteristics and firing behaviors in our network models approximated those determined experimentally. Our models distinguish between regimes in which OLM cells minimally or strongly affect the power of network oscillations, and predict that the dis-inhibitory effect of OLM cells on BSC to pyramidal cell interactions plays a critical role in the power of network theta oscillations. When OLM to BSC model connections are not too strong, the OLM cells’ direct influence on pyramidal cells balances with its indirect dis-inhibitory effect (through the BSCs). In this case, when the OLM cell population is silenced, there is a compensatory effect on network power, and thus minimal change in power. However, when these OLM to BSC connections are stronger, the dis-inhibition of pyramidal cells does not balance with their direct influence, and thus silencing OLM cells has a stronger effect. This does not change when we consider various distributions of strengths in which the cell populations affect the LFP. Thus, our network models are able to make particular predictions that can be tested with optogenetics.

CPP alters theta/gamma oscillations in rat hippocampus: simulation and experiment

Several different NMDA receptor (NMDAR) antagonists are used to produce pharmacological models for schizophrenia. These antagonists have different molecular mechanisms of action: non-competitive (e.g. ketamine, which binds at a site different from glutamate) and competitive (e.g. CPP, which displaces glutamate). Because competitive antagonism results in more glutamate availability, this may result in glutamate spill-over either onto other receptors of the same synapse or to neighboring synapses. In this study, we modeled the effects of competitive blockade by simultaneously blocking NMDAR and increasing activity of AMPAR (spillover). We looked at alterations of network oscillations and synchronization using our biophysical model of the CA1 region of hippocampus using the NEURON simulator. We then compared the results with data obtained from the CA1 region of hippocampus in rats injected with CPP. Our network consisted of 800 five-compartment pyramidal cells (PYR), 200 one-compartment basket cell interneurons (BAS), and 200 one-compartment oriens lacunosum-moleculare interneurons (OLM) [1]. All cells contained leak current, transient sodium current and delayed rectifier current. Additionally, pyramidal cells contained potassium type A current and pyramidal and OLM cells had Ih current. Cell classes were interconnected probabilistically with AMPA/NMDA synapses, and two classes of GABAa synapses. The OLM cells formed synapses on the distal dendrites of pyramidal cells, while the basket cells synapsed proximally on pyramidal and other basket cells. Pyramidal cells synapsed on both types of interneurons with AMPA/NMDA synapses. All synapses were bombarded with external Poisson inputs to generate network activity. Competitive inhibition was modeled by setting the conductance across NMDAR to zero, and increasing current conductance across AMPAR on the same set of synapses. We modeled this on synaptic sites on all cell populations. Also, given the possible variation of the affinity of competitive inhibitors to NMDAR on different cells, we studied this effect when it took place at the receptors of the 3 different cell populations separately. Experimental recordings were made from tetrode arrays implanted in the CA1 region of Long Evans rats chasing sugar pellets in a box. CPP at a dose of 5 mg/kg was injected intraperitoneally in the rats. Recordings were for 16 min sessions, separated by 30 min breaks during which the rats were returned to their cages. Recordings from CA1 of rat hippocampus under the effect of CPP, showed that there is a reduction in theta and an increase in gamma. Modeling competitive inhibition to glutamate at all synapse locations (on OLM, BAS, and PYR) resulted in a reduction in the theta power and an increase in gamma power, differing from the noncompetitive effect with ketamine, which reduced both theta and gamma when given across all synapses. However, this result was also seen when the effect of competitive inhibition was restricted to only OLM cell NMDARs. Therefore, our model demonstrates both of these interpretations of CPP action. We will examine further correlates between simulation and experiment to reduce this uncertainty.

Hub GABA Neurons Mediate Gamma-Frequency Oscillations at Ictal-like Event Onset in the Immature Hippocampus

Gamma-frequency oscillations (GFOs, >40Hz) are a general network signature at seizure onset at all stages of development, with possible deleterious consequences in the immature brain. At early developmental stages, the simultaneous occurrence of GFOs in different brain regions suggests the existence of a long-ranging synchronizing mechanism at seizure onset. Here, we show that hippocamposeptal (HS) neurons, which are GABA long-range projection neurons, are mandatory to drive the firing of hippocampal interneurons in a high-frequency regime at the onset of epileptiform discharges in the intact, immature septohippocampal formation. The synchronized firing of interneurons in turn produces GFOs, which are abolished after the elimination of a small number of HS neurons. Because they provide the necessary fast conduit for pacing large neuronal populations and display intra- and extrahippocampal long-range projections, HS neurons appear to belong to the class of hub cells that play a crucial role in the synchronization of developing networks.

Inhibitory control of hippocampal inhibitory neurons

Information processing within neuronal networks is determined by a dynamic partnership between principal neurons and local circuit inhibitory interneurons. The population of GABAergic interneurons is extremely heterogeneous and comprises, in many brain regions, cells with divergent morphological and physiological properties, distinct molecular expression profiles, and highly specialized functions. GABAergic interneurons have been studied extensively during the past two decades, especially in the hippocampus, which is a relatively simple cortical structure. Different types of hippocampal inhibitory interneurons control spike initiation [e.g., axo-axonic and basket cells (BCs)] and synaptic integration (e.g., bistratified and oriens–lacunosum moleculare interneurons) within pyramidal neurons and synchronize local network activity, providing a means for functional segregation of neuronal ensembles and proper routing of hippocampal information. Thus, it is thought that, at least in the hippocampus, GABAergic inhibitory interneurons represent critical regulating elements at all stages of information processing, from synaptic integration and spike generation to large-scale network activity. However, this raises an important question: if inhibitory interneurons are fundamental for network computations, what are the mechanisms that control the activity of the interneurons themselves? Given the essential role of synaptic inhibition in the regulation of neuronal activity, it would be logical to expect that specific inhibitory mechanisms have evolved to control the operation of interneurons. Here, we review the mechanisms of synaptic inhibition of interneurons and discuss their role in the operation of hippocampal inhibitory circuits.

Age‐dependent remodelling of inhibitory synapses onto hippocampal CA1 oriens‐lacunosum moleculare interneurons

Stratum oriens-lacunosum moleculare interneurons (O-LM INs) represent the major element of the hippocampal feedback inhibitory circuit, which provides inhibition to the distal dendritic sites of CA1 pyramidal neurons. Although the intrinsic conductance profile and the properties of glutamatergic transmission to O-LM INs have become a subject of intense investigation, far less is known about the properties of the inhibitory synapses formed onto these cells. Here, we used whole-cell patch-clamp recordings in acute mouse hippocampal slices to study the properties and plasticity of GABAergic inhibitory synapses onto O-LM INs. Surprisingly, we found that the kinetics of inhibitory postsynaptic currents (IPSCs) were slower in mature synapses (P26-40) due to the synaptic incorporation of the α5 subunit of the GABA(A) receptor (a5-GABA(A)R). Moreover, this age-dependent synaptic expression of a5-GABA(A)Rs was directly associated with the emergence of long-term potentiation at IN inhibitory synapses. Finally, the slower time course of IPSCs observed in O-LM INs of mature animals had a profound effect on IN excitability by significantly delaying its spike firing. Our data suggest that GABAergic synapses onto O-LM INs undergo significant modifications during postnatal maturation. The developmental switch in IPSC properties and plasticity is controlled by the synaptic incorporation of the a5-GABA(A)R subunit and may represent a potential mechanism for the age-dependent modifications in the inhibitory control of the hippocampal feedback inhibitory circuit.

HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path.

Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1 pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2(-/-)) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons in wild-type but not HCN2(-/-) mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons.

Role of ionotropic glutamate receptors in LTP in rat hippocampal CA1 oriens-lacunosum moleculare interneurons

Event Abstract Back to Event Role of ionotropic glutamate receptors in LTP in rat hippocampal CA1 oriens-lacunosum moleculare interneurons Iris Oren1, Wiebke Nissen2, Dimitri M. Kullmann1, Peter Somogyi3 and Karri Lamsa2* 1 UCL Institute of Neurology, University College London, United Kingdom 2 Department of Pharmacology, Oxford University, United Kingdom 3 MRC Anatomical Neuropharmacology Unit, Oxford University, United Kingdom Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) that is induced by presynaptic glutamate release when the postsynaptic membrane potential is hyperpolarized. This ‘anti-Hebbian’ form of LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate receptors. Although both AMPA and kainate receptors are expressed in hippocampal interneurons, their relative roles in anti-Hebbian LTP are not known. Because interneuron diversity potentially conceals simple rules underlying different forms of plasticity, we focus on glutamatergic synapses onto a subset of interneurons with dendrites in stratum oriens and a main ascending axon that projects to stratum lacunosum-moleculare, the O-LM cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent induction and expression properties, and is prevented by selective inhibition of AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in these cells is mediated by inwardly rectifying Ca2+ -permeable AMPA receptors. Although GluR5-containing kainate receptors contribute to synaptic currents at high stimulus frequency, they are not required for LTP induction. Glutamatergic synapses on O-LM cells thus behave in a homogeneous manner, and exhibit LTP dependent on Ca2+-permeable AMPA receptors. Restricting attention to an identified pathway within the hippocampal inhibitory circuitry thus reveals a far more uniform pattern of synaptic physiology, pharmacology and plasticity than seen in the population of interneurons as a whole. Sampling across interneuron types could explain some of the heterogeneity reported in previous studies on plasticity in which interneuron types were not identified. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Research on the cerebral cortex and related structures Citation: Oren I, Nissen W, Kullmann DM, Somogyi P and Lamsa K (2009). Role of ionotropic glutamate receptors in LTP in rat hippocampal CA1 oriens-lacunosum moleculare interneurons. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.210 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Mar 2009; Published Online: 06 Mar 2009. * Correspondence: Karri Lamsa, Department of Pharmacology, Oxford University, Oxford, United Kingdom, klamsa@bio.u-szeged.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Iris Oren Wiebke Nissen Dimitri M Kullmann Peter Somogyi Karri Lamsa Google Iris Oren Wiebke Nissen Dimitri M Kullmann Peter Somogyi Karri Lamsa Google Scholar Iris Oren Wiebke Nissen Dimitri M Kullmann Peter Somogyi Karri Lamsa PubMed Iris Oren Wiebke Nissen Dimitri M Kullmann Peter Somogyi Karri Lamsa Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Cell Type-Specific Tuning of Hippocampal Interneuron Firing during Gamma OscillationsIn Vivo

Cortical gamma oscillations contribute to cognitive processing and are thought to be supported by perisomatic-innervating GABAergic interneurons. We performed extracellular recordings of identified interneurons in the hippocampal CA1 area of anesthetized rats, revealing that the firing patterns of five distinct interneuron types are differentially correlated to spontaneous gamma oscillations. The firing of bistratified cells, which target dendrites of pyramidal cells coaligned with the glutamatergic input from hippocampal area CA3, is strongly phase locked to field gamma oscillations. Parvalbumin-expressing basket, axo-axonic, and cholecystokinin-expressing interneurons exhibit moderate gamma modulation, whereas the spike timing of distal dendrite-innervating oriens-lacunosum moleculare interneurons is not correlated to field gamma oscillations. Cholecystokinin-expressing interneurons fire earliest in the gamma cycle, a finding that is consistent with their suggested function of thresholding individual pyramidal cells. Furthermore, we show that field gamma amplitude correlates with interneuronal spike-timing precision and firing rate. Overall, our recordings suggest that gamma synchronization in vivo is assisted by temporal- and domain-specific GABAergic inputs to pyramidal cells and is initiated in pyramidal cell dendrites in addition to somata and axon initial segments.