Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor

Mikulovic, Sanja; Restrepo, Carlos E.; Siwani, Samer; Bauer, Pavol; Pupe, Stéfano; Tort, Adriano Bretanha Lopes; Kullander, Klas; Leão, Richardson N.

doi:10.1038/s41467-018-05907-w

Cited by 99 publications

(99 citation statements)

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“…Therefore, one possibility is that the low-theta oscillations we observed are indeed related to the rodent Type 2 theta, but this signal in humans has a broader functional role beyond anxiety, perhaps including episodic memory and other types of cognitive processes that involve the anterior hippocampus (Bannerman et al, 2004; Mitchell et al, 2008). Our interpretation is consistent with the recent finding that slower, Type 2 theta oscillations in rodents can be generated by a distinct network of cells in the ventral hippocampus (Mikulovic et al, 2018), which is homologous to the anterior hippocampus in humans (Colombo et al, 1988; Amaral & Witter, 1989; Moser & Moser, 1998; Strange et al, 2014).…”

Section: Discussionsupporting

confidence: 93%

Functionally distinct high and low theta oscillations in the human hippocampus

Goyal

Miller

Qasim

et al. 2018

Preprint

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22Based on rodent models, researchers have theorized that the hippocampus supports episodic 23 memory and navigation via the theta oscillation, a ∼4-10-Hz rhythm that coordinates brain-wide 24 neural activity. However, recordings from humans have indicated that hippocampal theta oscillations 25 are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in 26 theta's function. To characterize human hippocampal theta, we examined the properties of theta 27 oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects 28 performed a virtual spatial navigation task. During virtual movement, we observed hippocampal 29 oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently 30 displayed oscillations at ∼8-Hz and the precise frequency of these oscillations correlated with the 31 speed of movement, implicating these signals in spatial navigation. We also observed slower ∼3-Hz 32 oscillations, but these signals were more prevalent in the anterior hippocampus and their frequency 33 did not vary with movement speed. Our results converge with recent findings to suggest an updated 34 view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a 35 single general role, high-and low-theta oscillations, respectively, may reflect spatial and non-spatial 36 cognitive processes. 38The theta oscillation is a large-scale network rhythm that appears at ∼4-10 Hz in rodents and is 39 hypothesized to play a fundamental role in mammalian spatial navigation and memory (Kahana et 40 al., 2001; Buzsáki, 2005). However, in humans, there is mixed evidence regarding the relevance and 41 properties of hippocampal theta. Some studies in humans show hippocampal oscillations at 1-5 Hz that 42 have similar functional properties as the theta oscillations seen in rodents (e.g., Arnolds et al., 1980; 43 There is also evidence that human movement-related hippocampal theta oscillations vary substantially 45 in frequency according to whether a subject is in a physical or virtual environment (Aghajan et al., 2016; 46 Bohbot et al., 2017; Yassa, 2018). Together, these studies have been interpreted to suggest that the 47 human hippocampus does show a signal analogous to theta oscillations observed in rodents but that 48 this oscillation is more variable and slower in frequency (Jacobs, 2014). These apparent discrepancies 49 in the frequency of theta between species and behaviors shed doubt on the notion that theta exists as 50 a single general oscillatory phenomenon that coordinates brain-wide neural activity consistently across 51 species and tasks. 52Our study aimed to resolve these discrepancies by characterizing the properties of human hip-53 pocampal oscillations in spatial cognition. We analyzed intracranial electroencephalographic (iEEG) 54 recordings from the hippocampi of fourteen neurosurgical subjects performing a virtual-reality (VR) 55 spatial navigation task, in which subjects were aske...

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Section: Discussionsupporting

confidence: 93%

Functionally distinct high and low theta oscillations in the human hippocampus

Goyal

Miller

Qasim

et al. 2018

Preprint

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“…In conclusion, our data reveal the preferential recruitment of IS3 cells specifically during theta oscillations. Thus, a slow inhibition provided by these cells to OLM interneurons via the α5 GABA A receptor-containing synapses [73,74] may be responsible for pacing the OLM activity at theta frequency and generation of theta-oscillations (e.g., type II theta associated with the emotional context and generated in ventral hippocampus) [29].…”

Section: Discussionmentioning

confidence: 99%

“…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

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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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“…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

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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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Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor

Cited by 99 publications

References 61 publications

Functionally distinct high and low theta oscillations in the human hippocampus

Functionally distinct high and low theta oscillations in the human 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

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