Dendritic inhibition mediated by O-LM and bistratified interneurons in the hippocampus

Müller, Christina; Remy, Stefan

doi:10.3389/fnsyn.2014.00023

Cited by 67 publications

(98 citation statements)

References 153 publications

(314 reference statements)

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“…We observed a ~40% decrease in the frequency of excitatory synaptic response in these interneurons, suggestive of a dramatic decrease in the number or release probability of excitatory synapses on these cells, which likely disrupts their ability to regulate the timing and plasticity of pyramidal neuron activity (Muller and Remy, 2014). This shared deficit in excitatory synaptic response is unique to interneurons, as excitatory-to-excitatory neuron events (sEPSCs) are decreased in Null but increased in Tg1 mice.…”

Section: Discussionmentioning

confidence: 92%

“…We therefore tested this possibility in hippocampal CA1 oriens-layer interneurons, the majority of which receive excitatory glutamatergic input from the axon collaterals of CA1 pyramidal neurons and mediate feedback dendritic inhibition to these pyramidal neurons (Muller and Remy, 2014) (Figures 3A and 3B). Remarkably, the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in oriens-layer interneurons was decreased by about 40% in both Null and Tg1 mice (Figure 3B), revealing a profound impairment in excitatory synaptic response in the inhibitory neurons of the hippocampal circuit.…”

Section: Resultsmentioning

confidence: 99%

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Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model

Lü

Ash

et al. 2016

Neuron

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SUMMARY Loss- and gain-of-function mutations in Methyl-CpG-binding protein 2 (MECP2) underlie two distinct neurological syndromes with strikingly similar features, but the synaptic and circuit-level changes mediating these shared features are undefined. Here we report three novel signs of neural circuit dysfunction in three mouse models of MECP2 disorders (constitutive Mecp2-null, mosaic Mecp2+/−, and MECP2-duplication): abnormally elevated synchrony in the firing activity of hippocampal CA1 pyramidal neurons, an impaired homeostatic response to perturbations of excitatory-inhibitory balance, and decreased excitatory synaptic response in inhibitory neurons. Conditional mutagenesis studies revealed that MeCP2 dysfunction in excitatory neurons mediated elevated synchrony at baseline, while MeCP2 dysfunction in inhibitory neurons increased susceptibility to hyper-synchronization in response to perturbations. Chronic forniceal deep brain stimulation (DBS), recently shown to rescue hippocampus-dependent learning and memory in Mecp2+/− (Rett) mice, also rescued all three features of hippocampal circuit dysfunction in these mice.

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Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model

Lü

Ash

et al. 2016

Neuron

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“…Herein, we differentiate the percentages of CA1 PV-expressing cells by CA1 layer and by SSTco-expression, allowing for delineation of CA1 cell types (PV+ interneurons including bistratified and oriens-lacunosum-moleculare (O-LM) cells; Kosaka et al 1987; Buhl et al 1994; Masliah et al 1992; Freund and Buzsáki 1996; Jinno and Kosaka 2000, 2002a; Klausberger et al 2004; Klausberger and Somogyi 2008; Müller and Remy 2014; Yamada and Jinno 2015). Bistratified cells were discerned from O-LM interneurons via the relative intensity of PV (high in bistratified) and SST (minimal in bistratified) immunoreactivity.…”

Section: Discussionmentioning

confidence: 99%

“…Bistratified cells were discerned from O-LM interneurons via the relative intensity of PV (high in bistratified) and SST (minimal in bistratified) immunoreactivity. In contrast, O-LMs exert an opposing PV/SST profile, with a subset of O-LMs being entirely PV− (Chittajallu et al 2013; Müller and Remy 2014). Our data show a modest effect of Tat on the total PV+ population of the stratum pyramidale; however, this was not restricted to a particular PV+ cell type.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

et al. 2016

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Memory deficits are characteristic of HIV-associated neurocognitive disorders (HAND) and co-occur with hippocampal pathology. The HIV-1 transactivator of transcription (Tat), a regulatory protein, plays a significant role in these events, but the cellular mechanisms involved are poorly understood. Within the hippocampus, diverse populations of interneurons form complex networks; even subtle disruptions can drastically alter synaptic output, resulting in behavioral dysfunction. We hypothesized that HIV-1 Tat would impair cognitive behavior and injure specific hippocampal interneuron subtypes. Male transgenic mice that inducibly expressed HIV-1 Tat (or non-expressing controls) were assessed for cognitive behavior or had hippocampal CA1 subregions evaluated via interneuron subpopulation markers. Tat exposure decreased spatial memory in a Barnes maze and mnemonic performance in a novel object recognition test. Tat reduced the percentage of neurons expressing neuronal nitric oxide synthase (nNOS) without neuropeptide Y immunoreactivity in the stratum pyramidale and the stratum radiatum, parvalbumin in the stratum pyramidale, and somatostatin in the stratum oriens, which are consistent with reductions in interneuron-specific interneuron type 3 (IS3), bistratified, and oriens-lacunosum-moleculare interneurons, respectively. The findings reveal that an interconnected ensemble of CA1 nNOS-expressing interneurons, the IS3 cells, as well as subpopulations of parvalbumin- and somatostatin-expressing interneurons are preferentially vulnerable to HIV-1 Tat. Importantly, the susceptible interneurons form a microcircuit thought to be involved in feedback inhibition of CA1 pyramidal cells and gating of CA1 pyramidal cell inputs. The identification of vulnerable CA1 hippocampal interneurons may provide novel insight into the basic mechanisms underlying key functional and neurobehavioral deficits associated with HAND.

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“…However, most of these studies were limited to the analysis of excitatory input interactions only. A recent set of studies started to reveal the role of inhibition in the control of dendritic supralinear processes, using localized pharmacology and the combination of optogenetic stimulation and recording methods (Müller et al, 2012; Pouille et al, 2013; Müller and Remy, 2014). To reveal the subtle role of non-PV+ neurons these interactions will have to be studied during different brains states and state transitions.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Realistic Synaptic Distribution and 3D Geometry on Signal Integration and Extracellular Field Generation of Hippocampal Pyramidal Cells and Inhibitory Neurons

Gulyás

Freund

Káli

2016

Front. Neural Circuits

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In vivo and in vitro multichannel field and somatic intracellular recordings are frequently used to study mechanisms of network pattern generation. When interpreting these data, neurons are often implicitly considered as electrotonically compact cylinders with a homogeneous distribution of excitatory and inhibitory inputs. However, the actual distributions of dendritic length, diameter, and the densities of excitatory and inhibitory input are non-uniform and cell type-specific. We first review quantitative data on the dendritic structure and synaptic input and output distribution of pyramidal cells (PCs) and interneurons in the hippocampal CA1 area. Second, using multicompartmental passive models of four different types of neurons, we quantitatively explore the effect of differences in dendritic structure and synaptic distribution on the errors and biases of voltage clamp measurements of inhibitory and excitatory postsynaptic currents. Finally, using the 3-dimensional distribution of dendrites and synaptic inputs we calculate how different inhibitory and excitatory inputs contribute to the generation of local field potential in the hippocampus. We analyze these effects at different realistic background activity levels as synaptic bombardment influences neuronal conductance and thus the propagation of signals in the dendritic tree. We conclude that, since dendrites are electrotonically long and entangled in 3D, somatic intracellular and field potential recordings miss the majority of dendritic events in some cell types, and thus overemphasize the importance of perisomatic inhibitory inputs and belittle the importance of complex dendritic processing. Modeling results also suggest that PCs and inhibitory neurons probably use different input integration strategies. In PCs, second- and higher-order thin dendrites are relatively well-isolated from each other, which may support branch-specific local processing as suggested by studies of active dendritic integration. In the electrotonically compact parvalbumin- and cholecystokinincontaining interneurons, synaptic events are visible in the whole dendritic arbor, and thus the entire dendritic tree may form a single integrative element. Calretinin-containing interneurons were found to be electrotonically extended, which suggests the possibility of complex dendritic processing in this cell type. Our results also highlight the need for the integration of methods that allow the measurement of dendritic processes into studies of synaptic interactions and dynamics in neural networks.

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Dendritic inhibition mediated by O-LM and bistratified interneurons in the hippocampus

Cited by 67 publications

References 153 publications

Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model

Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

The Effects of Realistic Synaptic Distribution and 3D Geometry on Signal Integration and Extracellular Field Generation of Hippocampal Pyramidal Cells and Inhibitory Neurons

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