Chandelier Cells in Functional and Dysfunctional Neural Circuits

Wang, Yiqing; Zhang, Peng; Wyskiel, Daniel R.

doi:10.3389/fncir.2016.00033

Cited by 27 publications

(35 citation statements)

References 121 publications

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“…A role for AIS abnormalities in epilepsy has been suggested in other studies 55 – 57 , implicating trafficking and localization of voltage-gated channels to the AIS. Other analyses have found alterations to AIS inhibitory synapses resulting from or contributing to epilepsy; however, both decreases and increases in AIS synapse number have been found, leaving the contribution of this synaptic subtype unclear 58 – 60 . Our results directly link a mutation in a specific GABA A R-subunit, accompanied by an alteration in AIS GABAergic synapses, to an epileptic phenotype.…”

Section: Discussionmentioning

confidence: 95%

Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin

et al. 2018

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Fast inhibitory synaptic transmission is mediated by γ-aminobutyric acid type A receptors (GABAARs) that are enriched at functionally diverse synapses via mechanisms that remain unclear. Using isothermal titration calorimetry and complementary methods we demonstrate an exclusive low micromolar binding of collybistin to the α2-subunit of GABAARs. To explore the biological relevance of collybistin-α2-subunit selectivity, we generate mice with a mutation in the α2-subunit-collybistin binding region (Gabra2-1). The mutation results in loss of a distinct subset of inhibitory synapses and decreased amplitude of inhibitory synaptic currents. Gabra2–1 mice have a striking phenotype characterized by increased susceptibility to seizures and early mortality. Surviving Gabra2-1 mice show anxiety and elevations in electroencephalogram δ power, which are ameliorated by treatment with the α2/α3-selective positive modulator, AZD7325. Taken together, our results demonstrate an α2-subunit selective binding of collybistin, which plays a key role in patterned brain activity, particularly during development.

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Section: Discussionmentioning

confidence: 95%

Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin

et al. 2018

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“…These cells form vertically oriented clusters of axon terminals, called cartridges, giving them a chandelier-like appearance. A single pyramidal cell receives contacts from multiple chandelier cells 97 , forming an average of 3 to 5 boutons each 98 depending on the brain region 99 and age 100 . The synapses are enriched for the GABAAα2 receptor subunit 101 , 102 and pre-synaptically express the high-affinity GABA transporter 1 (GAT1) 103 .…”

Section: The Central Role Of Parvalbumin-positive Interneurons In E/imentioning

confidence: 99%

“…Since their discovery, there has been a debate about the actions of chandelier cells (reviewed by Wang and colleagues 98 ). Some studies using brain slice recordings showed a depolarizing 108 and even excitatory 109 action for these interneurons, whereas others report an inhibitory action 110 .…”

Section: The Central Role Of Parvalbumin-positive Interneurons In E/imentioning

confidence: 99%

“…As a result, a limited number of studies focus on chandelier cells but instead report on PV interneurons in general, or PV basket cells, which provide a more accessible target of study because of their relative abundance ( Figure 1 ). Nonetheless, chandelier cells are considered to play an important role in psychiatric disorders 11 , 98 , 119 , and the development of strategies to specifically target this interneuron subtype would be an important step towards understanding the role of these interneurons.…”

Section: The Central Role Of Parvalbumin-positive Interneurons In E/imentioning

confidence: 99%

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Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders

2018

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Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.

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“…On the other hand, excitatory PVChCs would support the hypothesis of insufficient excitation between pyramidal cells, with a homeostatic reduction of PVBC inhibition and an increase in excitation by PVChCs as compensatory mechanisms. The question of whether PVChCs have excitatory effects on principal cells in adult in vivo brain is not yet settled …”

Section: The Gabaergic System and Excitation/inhibition Disbalance Inmentioning

confidence: 99%

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

et al. 2019

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Despite the substantial knowledge accumulated by past research, the exact mechanisms of the pathogenesis of schizophrenia and causal treatments still remain unclear. Deficits of cognition and information processing in schizophrenia are today often viewed as the primary and core symptoms of this devastating disorder. These deficits likely result from disruptions in the coordination of neuronal and neural activity. The aim of this review is to bring together convergent evidence of discoordinated brain circuits in schizophrenia at multiple levels of resolution, ranging from principal cells and interneurons, neuronal ensembles and local circuits, to large-scale brain networks. We show how these aberrations could underlie deficits in cognitive control and other higher order cognitive-behavioural functions. Converging evidence from both animal models and patients with schizophrenia is presented in an effort to gain insight into common features of deficits in the brain information processing in this disorder, marked by disruption of several neurotransmitter and signalling systems and severe behavioural outcomes. K E Y W O R D SfMRI, GABA interneurons, humans, oscillations, psychosis, rats

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Chandelier Cells in Functional and Dysfunctional Neural Circuits

Cited by 27 publications

References 121 publications

Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin

Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin

Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

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