Parvalbumin-containing interneurons in rat hippocampus have an AMPA receptor profile suggestive of vulnerability to excitotoxicity

Moga, Diana; Hof, Patrick R.; Vissavajjhala, Prabhakar; Moran, Thomas M.; Morrison, John H.

doi:10.1016/s0891-0618(02)00012-1

Cited by 30 publications

(25 citation statements)

References 7 publications

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“…Due to neuronal heterogeneity in the hippocampus (Bouilleret et al 2000; Moga et al 2002; Avignone et al 2005), differential responses to Tat-induced excitotoxicity and neuroinflammation may be expected. In a kainate-induced model of excitotoxicity, a loss of GAT-1, a GABA reuptake protein, was greater in the stratum pyramidale than in the stratum oriens and the stratum radiatum, suggesting regional variability in selective vulnerability of hippocampal interneurons (Bouilleret et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Hippocampal interneurons interact as part of a functional network and it is clear that the removal of even one cell type from the network can have drastic effects on information processing, pyramidal cell excitation, and consequent behavioral outcomes (Moga et al 2002; Dugladze et al 2007; Goldin et al 2007; Tóth et al 2010; Peng et al 2013; Long et al 2014; Lovett-Barron et al 2014; Lovett-Barron and Losonczy 2014; Tóth and Maglóczky 2014; Orbán-Kris et al 2015). Importantly, the susceptible nNOS+/NPY− interneurons of the stratum pyramidale and the stratum radiatum, PV+ cells of the stratum pyramidale, and SST+ interneurons of the stratum oriens form a microcircuit known to be involved in a complex feedback loop/input gating mechanism that regulates network synchronization within CA1 (Fig.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Studies have indicated that the density of inputs and the total number of afferent synapses are several times higher on PV cells than on CB or CR cells, whereas the ratio of inhibitory inputs is significantly higher on CB and CR cells [40] , suggesting that PV-positive neurons receive more excitatory inputs than CB-and CR-positive neurons and thus are more vulnerable to excitotoxic damage. The AMPA receptor subunit GluR3 in PV-containing interneurons is highly expressed in the hippocampus and neocortex, whereas GluR2 is not observed, indicating that this is likely to contribute to the selective vulnerability of these interneurons to excitotoxicity [41] .…”

Section: Pv-immunoreactive (Pv-ir) Interneurons Arementioning

confidence: 99%

Dysfunction of hippocampal interneurons in epilepsy

Liu

et al. 2014

Neurosci. Bull.

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Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy.

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“…Under pathologic conditions, the activation of ionotropic glutamate receptors with high Ca 2 þ -permeability and/or alterations in parvalbumin expression in fast-spiking interneurons might result in cytosolic and mitochondrial Ca 2 þ -overload that would also enhance the generation of ROS and nitric oxide. 173,[178][179][180] Enhanced ROS generation combined with alterations of antioxidative mechanisms may finally cause higher levels of oxidative stress in fast-spiking interneurons as compared with other neuron subtypes, with devastating consequences on nuclear and mitochondrial DNA and/or functional proteins such as enzymes and ion channels. 173,[181][182][183][184] These putative pathophysiological mechanisms in fast-spiking interneurons, i.e., higher susceptibility to metabolic and oxidative stress, might apply to several neurologic and psychiatric disorders that go along with chronic mitochondrial dysfunction and/or chronic cerebral hypoperfusion (Figure 3).…”

Section: Perspective: Metabolic and Oxidative Stress In Fast-spiking mentioning

confidence: 99%

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

Kann

Papageorgiou

Draguhn

2014

J Cereb Blood Flow Metab

211

228

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Gamma oscillations (B30 to 100 Hz) provide a fundamental mechanism of information processing during sensory perception, motor behavior, and memory formation by coordination of neuronal activity in networks of the hippocampus and neocortex. We review the cellular mechanisms of gamma oscillations about the underlying neuroenergetics, i.e., high oxygen consumption rate and exquisite sensitivity to metabolic stress during hypoxia or poisoning of mitochondrial oxidative phosphorylation. Gamma oscillations emerge from the precise synaptic interactions of excitatory pyramidal cells and inhibitory GABAergic interneurons. In particular, specialized interneurons such as parvalbumin-positive basket cells generate action potentials at high frequency ('fast-spiking') and synchronize the activity of numerous pyramidal cells by rhythmic inhibition ('clockwork'). As prerequisites, fast-spiking interneurons have unique electrophysiological properties and particularly high energy utilization, which is reflected in the ultrastructure by enrichment with mitochondria and cytochrome c oxidase, most likely needed for extensive membrane ion transport and g-aminobutyric acid metabolism. This supports the hypothesis that highly energized fast-spiking interneurons are a central element for cortical information processing and may be critical for cognitive decline when energy supply becomes limited ('interneuron energy hypothesis'). As a clinical perspective, we discuss the functional consequences of metabolic and oxidative stress in fast-spiking interneurons in aging, ischemia, Alzheimer's disease, and schizophrenia.

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Parvalbumin-containing interneurons in rat hippocampus have an AMPA receptor profile suggestive of vulnerability to excitotoxicity

Cited by 30 publications

References 7 publications

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

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

Dysfunction of hippocampal interneurons in epilepsy

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

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