OLMα2 Cells Bidirectionally Modulate Learning

Siwani, Samer; França, Arthur S. C.; Mikulovic, Sanja; Reis, Amilcar; Hilscher, Markus M.; Edwards, Steven J; Leão, Richardson N.; Tort, Adriano Bretanha Lopes; Kullander, Klas

doi:10.1016/j.neuron.2018.06.022

Cited by 53 publications

(41 citation statements)

References 48 publications

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“…The OLM cells are known to fire at the trough of theta oscillation, but can be silent during the sharp wave-associated ripples (SWRs) via yet unknown mechanisms [4][5][6][7]19]. By inhibiting distal and disinhibiting proximal dendrites of CA1 PCs, OLM cells have been considered essential for modulating the integration of the temporoammonic (TA) vs Schaffer collaterals (SC) inputs [20][21][22][23], burst firing of PCs [24,25] and generation of theta oscillations in vitro [26][27][28] and in vivo in the ventral hippocampus [29]. Thus, given that synchronous activation of IS3 cells is capable of pacing the OLM interneuron activity at theta frequency [18], the IS3 input to OLM cells may act as a gear mechanism providing for rhythmic gating of the SC vs TA inputs in the CA1 area.…”

Section: Introductionmentioning

confidence: 99%

Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus

Luo

Guet-McCreight

Villette

et al. 2018

Preprint

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In the hippocampus, a highly specialized population of vasoactive intestinal peptide (VIP)-expressing interneuron-specific (IS) inhibitory cells provides local circuit disinhibition via preferential innervation of different types of GABAergic interneurons.While disinhibition can be critical in modulating network activity and different forms of hippocampal learning, the synaptic and integrative properties of IS cells and their recruitment during network oscillations remain unknown. Using a combination of patchclamp recordings, photostimulation, computational modelling as well as recordings of network oscillations simultaneously with two-photon Ca 2+ -imaging in awake mice in vivo, we identified synaptic mechanisms that can control the firing of IS cells, and explored their impact on the cell recruitment during theta oscillations and sharp-waveassociated ripples. We found that IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, integrating their intrinsic and synaptic properties into computational models predicted recruitment of these cells during the rising to peak phases of theta oscillations and during ripples depending on inhibitory contributions. In vivo Ca 2+ -imaging in awake mice confirmed in part the theoretical predictions, revealing a significant speed modulation of IS cells and their preferential albeit delayed recruitment during theta-run epochs, with firing at the rising phase to peak of the theta cycle. However, it also uncovered that IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.3

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Section: Introductionmentioning

confidence: 99%

Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus

Luo

Guet-McCreight

Villette

et al. 2018

Preprint

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“…It has been proposed that OLM cells play a gating role ( Leão et al, 2012 ), akin to earlier work by Blasco-Ibáñez and Freund (1995) who showed that “horizontal SOM+ interneurons” (i.e., putative OLM cells) could act as a switch controlling activation of local pyramidal cells via Schaeffer collaterals or perforant path input from entorhinal cortex. Further work has shown that OLM cells in intermediate regions of CA1 exert a bidirectional control on learning and memory ( Siwani et al, 2018 ), and ventral OLM cells control Type 2 theta rhythms and are associated with increased risk-taking ( Mikulovic et al, 2018 ). In a recent modeling study, OLM cells were shown to be critical in producing a robust intrinsic theta output ( Chatzikalymniou and Skinner, 2018 ), which suggests that their neuromodulation may be key to the maintenance of theta rhythms.…”

Section: Discussionmentioning

confidence: 99%

Somatodendritic HCN channels in hippocampal OLM cells revealed by a convergence of computational models and experiments

Sekulić

Garrett

et al. 2019

Preprint

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Somatodendritic HCN channels in1 hippocampal OLM cells revealed by a 2 convergence of computational 3 Abstract 22Determining details of spatially extended neurons is a challenge that needs to be overcome. The 23 oriens-lacunosum/moleculare (OLM) interneuron has been implicated as a critical controller of 24 hippocampal memory making it essential to understand how its biophysical properties contribute 25 to function. We previously used computational models to show that OLM cells exhibit theta spiking 26 resonance frequencies that depend on their dendrites having hyperpolarization-activated cation 27 channels (h-channels). However, whether OLM cells have dendritic h-channels is unknown. We 28 performed a set of whole-cell recordings of OLM cells from mouse hippocampus and constructed 29 multi-compartment models using morphological and electrophysiological parameters extracted 30 from the same cell. The models matched experiments only when dendritic h-channels were 31 present. Immunohistochemical localization of the HCN2 subunit confirmed dendritic expression. 32 These models can be used to obtain insight into hippocampal function. Our work shows that a tight 33 integration of model and experiment tackles the challenge of characterizing spatially extended 34 neurons. 35 36 1 of 40 2 of 40 Manuscript submitted to eLife invasively investigating the biophysical characteristics of fine dendritic compartments. However, 87 dendrites are where most synaptic contacts are made and where signal integration in neurons 88 occurs (Stuart and Spruston, 2015). Thus, these aspects must be tackled along with considerations 89 of cellular variability. 90 In this work we focus on the oriens-lacunosum/moleculare (OLM) cell, an identified inhibitory 91 cell type in the hippocampal CA1 area (Maccaferri and Lacaille, 2003; Müller and Remy, 2014). OLM 92 cells receive excitatory glutamatergic input predominantly from local CA1 pyramidal neurons and 93 form GABAergic synapses onto the distal dendrites of CA1 pyramidal neurons, as well as onto 94 other CA1 inhibitory cells (Blasco-Ibáñez and Freund, 1995; Klausberger, 2009; Leão et al., 2012; 95 Maccaferri et al., 2000). Functionally, proposed roles of OLM cells include gating sensory and 96 contextual information in CA1 (Leão et al., 2012), and supporting the acquisition of fear memories 97 (Lovett-Barron et al., 2014). Moreover, OLM cell firing is phase-locked to the prominent theta 98 rhythms in the hippocampus of behaving animals (Katona et al., 2014; Klausberger et al., 2003; 99 Klausberger and Somogyi, 2008; Varga et al., 2012). Although it has long been known that OLM 100 cells express hyperpolarization-activated cation channels (h-channels) (Maccaferri and McBain, 101 1996), it is still unclear whether these channels are present in their dendrites. From a functional 102 perspective, the consequences of dendritic h-channel expression in OLM cells was explored in our 103previous computational study where h-channels were found to modulate the spiking preference of 104 OLM cell ...

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“…On the other hand, a recent study found CA1 OLM cells to follow theta‐frequency inputs independently of I h (Kispersky, Fernandez, Economo, & White, ). However, the aforementioned studies do not report the specific location of investigated OLM cells along the dorsoventral hippocampal axis, while a recent study (Siwani et al, ) demonstrated that OLM α2 cells from the intermediate hippocampus show larger depolarization in response to nicotine than DH OLM α2 interneurons. These results indicate differential biophysical properties of OLM interneurons along the septotemporal hippocampal axis.…”

Section: Introductionmentioning

confidence: 95%

“…Modeling studies have suggested that oriens lacunosum moleculare (OLM) interneurons are essential to hippocampal theta rhythmogenesis through feedback inhibition (Hummos, Franklin, & Nair, ; Neymotin et al, ; Tort, Rotstein, Dugladze, Gloveli, & Kopell, ). OLM cells, together with bistratified cells that target different dendritic compartments of PCs than OLM cells (Müller & Remy, ), contribute to behaviors where gating of information is important for the functional output of the hippocampus (Katona et al, ; Leão et al, ; Lovett‐Barron et al, ; Mikulovic et al, ; Siwani et al, ). The OLM neuron is characterized based on its morphological features and slow accommodating firing (Leão et al, ), and recently several genetic markers have been evaluated for targeting OLM cells (Chittajallu et al, ; Leão et al, ; Mikulovic, Restrepo, Hilscher, Kullander, & Leão, ; Taniguchi et al, ).…”

Section: Introductionmentioning

confidence: 99%

Chrna2‐OLM interneurons display different membrane properties and h‐current magnitude depending on dorsoventral location

et al. 2019

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The hippocampus is an extended structure displaying heterogeneous anatomical cell layers along its dorsoventral axis. It is known that dorsal and ventral regions show different integrity when it comes to functionality, innervation, gene expression, and pyramidal cell properties. Still, whether hippocampal interneurons exhibit different properties along the dorsoventral axis is not known. Here, we report electrophysiological properties of dorsal and ventral oriens lacunosum moleculare (OLM) cells from coronal sections of the Chrna2‐cre mouse line. We found dorsal OLM cells to exhibit a significantly more depolarized resting membrane potential compared to ventral OLM cells, while action potential properties were similar between the two groups. We found ventral OLM cells to show a higher initial firing frequency in response to depolarizing current injections but also to exhibit a higher spike‐frequency adaptation than dorsal OLM cells. Additionally, dorsal OLM cells displayed large membrane sags in response to negative current injections correlating with our results showing that dorsal OLM cells have more hyperpolarization‐activated current (Ih) compared to ventral OLM cells. Immunohistochemical examination indicates the h‐current to correspond to hyperpolarization‐activated cyclic nucleotide‐gated subunit 2 (HCN2) channels. Computational studies suggest that Ih in OLM cells is essential for theta oscillations in hippocampal circuits, and here we found dorsal OLM cells to present a higher membrane resonance frequency than ventral OLM cells. Thus, our results highlight regional differences in membrane properties between dorsal and ventral OLM cells allowing this interneuron to differently participate in the generation of hippocampal theta rhythms depending on spatial location along the dorsoventral axis of the hippocampus.

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OLMα2 Cells Bidirectionally Modulate Learning

Cited by 53 publications

References 48 publications

Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus

Synaptic mechanisms underlying the network state-dependent recruitment of VIP-expressing interneuron-specific interneurons in the CA1 hippocampus

Somatodendritic HCN channels in hippocampal OLM cells revealed by a convergence of computational models and experiments

Chrna2‐OLM interneurons display different membrane properties and h‐current magnitude depending on dorsoventral location

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