scholarly journals Neuregulin-1 Regulates Cortical Inhibitory Neuron Dendrite and Synapse Growth through DISC1

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Brianna K. Unda ◽  
Vickie Kwan ◽  
Karun K. Singh
Keyword(s):  
Synapse Formation ◽  
Inhibitory Neuron ◽  
Inhibitory Interneuron ◽  
Dominant Negative ◽  
Inhibitory Neurons ◽  
Synaptic Growth ◽  
Neuregulin 1 ◽  
Neuron Dendrite ◽  
Independent Risk Factors ◽  
Developmental Signalling

Cortical inhibitory neurons play crucial roles in regulating excitatory synaptic networks and cognitive function and aberrant development of these cells have been linked to neurodevelopmental disorders. The secreted neurotrophic factor Neuregulin-1 (NRG1) and its receptor ErbB4 are established regulators of inhibitory neuron connectivity, but the developmental signalling mechanisms regulating this process remain poorly understood. Here, we provide evidence that NRG1-ErbB4 signalling functions through the multifunctional scaffold protein, Disrupted in Schizophrenia 1 (DISC1), to regulate the development of cortical inhibitory interneuron dendrite and synaptic growth. We found that NRG1 increases inhibitory neuron dendrite complexity and glutamatergic synapse formation onto inhibitory neurons and that this effect is blocked by expression of a dominant negative DISC1 mutant, or DISC1 knockdown. We also discovered that NRG1 treatment increases DISC1 expression and its localization to glutamatergic synapses being made onto cortical inhibitory neurons. Mechanistically, we determined that DISC1 binds ErbB4 within cortical inhibitory neurons. Collectively, these data suggest that a NRG1-ErbB4-DISC1 signalling pathway regulates the development of cortical inhibitory neuron dendrite and synaptic growth. Given that NRG1, ErbB4, and DISC1 are schizophrenia-linked genes, these findings shed light on how independent risk factors may signal in a common developmental pathway that contributes to neural connectivity defects and disease pathogenesis.

scholarly journals Implications of Extended Inhibitory Neuron Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes
Keyword(s):  
Neural Circuit ◽  
Inhibitory Neuron ◽  
Postnatal Period ◽  
Specific Pattern ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Neuron Development ◽  
Cortical Regions ◽  
Circuit Formation

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

scholarly journals Amyloid-β Oligomers Induce Only Mild Changes to Inhibitory Bouton Dynamics

2021 ◽  
Vol 5 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Marvin Ruiter ◽  
Christine Lützkendorf ◽  
Jian Liang ◽  
Corette J. Wierenga
Keyword(s):  
Hippocampal Slices ◽  
Inhibitory Neuron ◽  
Amyloid Β ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Amyloid Β Protein ◽  
Protein Precursor ◽  
Β Protein ◽  
Plaque Load ◽  
Early Alzheimer’S Disease

The amyloid-β protein precursor is highly expressed in a subset of inhibitory neuron in the hippocampus, and inhibitory neurons have been suggested to play an important role in early Alzheimer’s disease plaque load. Here we investigated bouton dynamics in axons of hippocampal interneurons in two independent amyloidosis models. Short-term (24 h) amyloid-β (Aβ)-oligomer application to organotypic hippocampal slices slightly increased inhibitory bouton dynamics, but bouton density and dynamics were unchanged in hippocampus slices of young-adult AppNL - F - G-mice, in which Aβ levels are chronically elevated. These results indicate that loss or defective adaptation of inhibitory synapses are not a major contribution to Aβ-induced hyperexcitability.

scholarly journals Lateral entorhinal cortex inputs modulate hippocampal dendritic excitability by recruiting a local disinhibitory microcircuit

2022 ◽  
Author(s):  
Olesia M Bilash ◽  
Spyridon Chavlis ◽  
Panayiota Poirazi ◽  
Jayeeta Basu
Keyword(s):  
Entorhinal Cortex ◽  
Pyramidal Neurons ◽  
Inhibitory Neuron ◽  
Inhibitory Neurons ◽  
Environmental Cues ◽  
Memory Processing ◽  
Ca1 Pyramidal Neurons ◽  
Dendritic Spikes ◽  
Hippocampal Area ◽  
Insight Into

The lateral entorhinal cortex (LEC) provides information about multi-sensory environmental cues to the hippocampus through direct inputs to the distal dendrites of CA1 pyramidal neurons. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. However, we know little about the functional circuit interactions between LEC and the hippocampus. In this study, we combine functional circuit mapping and computational modeling to examine how long-range glutamatergic LEC projections modulate compartment-specific excitation-inhibition dynamics in hippocampal area CA1. We demonstrate that glutamatergic LEC inputs can drive local dendritic spikes in CA1 pyramidal neurons, aided by the recruitment of a disinhibitory vasoactive intestinal peptide (VIP)-expressing inhibitory neuron microcircuit. Our circuit mapping further reveals that, in parallel, LEC also recruits cholecystokinin (CCK)-expressing inhibitory neurons, which our model predicts act as a strong suppressor of dendritic spikes. These results provide new insight into a cortically-driven GABAergic microcircuit mechanism that gates non-linear dendritic computations, which may support compartment-specific coding of multi-sensory contextual features within the hippocampus.

Epileptiform activity in microcultures containing one excitatory hippocampal neuron

1991 ◽  
Vol 65 (4) ◽  
pp. 761-770 ◽  
Author(s):  
M. M. Segal
Keyword(s):  
Action Potentials ◽  
Epileptiform Activity ◽  
Inhibitory Neuron ◽  
Excitatory Neuron ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Intracellular Recordings ◽  
Voltage Fluctuations ◽  
Excitatory Neurons ◽  
Small Voltage

1. Paroxysmal depolarizing shifts (PDSs) occur during interictal epileptiform activity. Sustained depolarizations are characteristic of ictal activity, and events resembling PDSs also occur during the sustained depolarizations. To study these elements of epileptiform activity in a simpler context, I used the in vitro chronic-excitatory-block model of epilepsy of Furshpan and Potter and the microculture technique of Segal and Furshpan. 2. Intracellular recordings were made from 93 single-neuron microcultures. Forty of these solitary neurons were excitatory, their action potentials were replaced by PDS-like events or sustained depolarizations as kynurenate was removed from the perfusion solution. PDS-like events were similar to PDSs in intact cortex, mass cultures, and microcultures with more than one neuron. Small voltage fluctuations were also seen in solitary excitatory neurons in the absence of recorded action potentials. Sustained depolarizations developed in 5 of the 40 excitatory neurons. Forty-eight of the 93 solitary neurons were inhibitory, with bicuculline-sensitive hyperpolarizations after the action potential (ascribable to gamma-aminobutyric acid-A autapses). None of the solitary inhibitory neurons displayed sustained depolarizations. Five of the 93 neurons were insensitive to both kynurenate and bicuculline and were not placed in either the excitatory or the inhibitory category. 3. Both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors contributed to the PDS-like events and sustained depolarizations. Only a non-NMDA glutamate receptor component was evident for the small voltage fluctuations. 4. Intracellular recordings were also made from two-neuron microcultures, each containing one excitatory neuron and one inhibitory neuron. Sustained depolarizations developed in five microcultures, in each case only in the excitatory neuron.

scholarly journals The Effect of Inhibitory Neuron on the Evolution Model of Higher-Order Coupling Neural Oscillator Population

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Qi ◽  
Rubin Wang ◽  
Xianfa Jiao ◽  
Ying Du
Keyword(s):  
Coupling Strength ◽  
Neural Coding ◽  
Inhibitory Neuron ◽  
Higher Order ◽  
Inhibitory Neurons ◽  
Neural Oscillator ◽  
Number Density ◽  
External Stimulation ◽  
Average Number Density ◽  
Inhibitory Coupling

We proposed a higher-order coupling neural network model including the inhibitory neurons and examined the dynamical evolution of average number density and phase-neural coding under the spontaneous activity and external stimulating condition. The results indicated that increase of inhibitory coupling strength will cause decrease of average number density, whereas increase of excitatory coupling strength will cause increase of stable amplitude of average number density. Whether the neural oscillator population is able to enter the new synchronous oscillation or not is determined by excitatory and inhibitory coupling strength. In the presence of external stimulation, the evolution of the average number density is dependent upon the external stimulation and the coupling term in which the dominator will determine the final evolution.

scholarly journals Specific Neuroligin3–αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Motokazu Uchigashima ◽  
Kohtarou Konno ◽  
Emily Demchak ◽  
Amy Cheung ◽  
Takuya Watanabe ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Synapse Formation ◽  
Glutamate Transporter ◽  
Inhibitory Interneuron ◽  
Synaptic Function ◽  
Inhibitory Synapses ◽  
Organotypic Slice Cultures ◽  
Splice Isoform ◽  
Synaptic Complexes ◽  
Signaling Interactions

Synapse formation and regulation require signaling interactions between pre- and postsynaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the functions of neuroligins (Nlgns), postsynaptic CAMs, rely on the formation of trans-synaptic complexes with neurexins (Nrxns), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated via Nrxn interactions is unknown. Here we demonstrate that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3-expressing (VGT3+) inhibitory terminals and regulates VGT3+ inhibitory interneuron-mediated synaptic transmission in mouse organotypic slice cultures. Gene expression analysis of interneurons revealed that the αNrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic αNrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn–Nrxn signaling generates distinct functional properties at synapses.

scholarly journals On the Validity of Neural Mass Models

2021 ◽  
Vol 14 ◽  
Author(s):  
Nicolás Deschle ◽  
Juan Ignacio Gossn ◽  
Prejaas Tewarie ◽  
Björn Schelter ◽  
Andreas Daffertshofer
Keyword(s):  
Mean Field ◽  
Low Frequency ◽  
Inhibitory Neuron ◽  
Inhibitory Neurons ◽  
Neural Population ◽  
Mass Model ◽  
Time Scale Separation ◽  
Neural Mass ◽  
The Mean ◽  
Parameter Ranges

Modeling the dynamics of neural masses is a common approach in the study of neural populations. Various models have been proven useful to describe a plenitude of empirical observations including self-sustained local oscillations and patterns of distant synchronization. We discuss the extent to which mass models really resemble the mean dynamics of a neural population. In particular, we question the validity of neural mass models if the population under study comprises a mixture of excitatory and inhibitory neurons that are densely (inter-)connected. Starting from a network of noisy leaky integrate-and-fire neurons, we formulated two different population dynamics that both fall into the category of seminal Freeman neural mass models. The derivations contained several mean-field assumptions and time scale separation(s) between membrane and synapse dynamics. Our comparison of these neural mass models with the averaged dynamics of the population reveals bounds in the fraction of excitatory/inhibitory neuron as well as overall network degree for a mass model to provide adequate estimates. For substantial parameter ranges, our models fail to mimic the neural network's dynamics proper, be that in de-synchronized or in (high-frequency) synchronized states. Only around the onset of low-frequency synchronization our models provide proper estimates of the mean potential dynamics. While this shows their potential for, e.g., studying resting state dynamics obtained by encephalography with focus on the transition region, we must accept that predicting the more general dynamic outcome of a neural network via its mass dynamics requires great care.

scholarly journals GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter

2021 ◽  
Author(s):  
Chiaki Hoshino ◽  
Ayumu Konno ◽  
Nobutake Hosoi ◽  
Ryosuke Kaneko ◽  
Ryo Mukai ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Fluorescent Protein ◽  
Critical Role ◽  
Inhibitory Neuron ◽  
Inhibitory Neurons ◽  
Acid Decarboxylase ◽  
Gabaergic Interneurons ◽  
Drug Induced ◽  
Whole Brain ◽  
Chandelier Cells

Abstract GABAergic interneurons play a critical role in tuning neural networks in the central nervous system, and their defects are associated with neuropsychiatric disorders. Currently, the mDlx enhancer is solely used for adeno-associated virus (AAV) vector-mediated transgene delivery into cortical interneurons. Here, we developed a new inhibitory neuron-specific promoter (designated as the mGAD65 promoter), with a length of 2.5 kb, from a mouse genome upstream of exon 1 of the Gad2 gene encoding glutamic acid decarboxylase (GAD) 65. Intravenous infusion of blood-brain barrier-penetrating AAV-PHP.B expressing an enhanced green fluorescent protein under the control of the mGAD65 promoter transduced the whole brain in an inhibitory neuron-specific manner. The specificity and efficiency of the mGAD65 promoter for GABAergic interneurons, which was assessed at the motor cortex, were almost identical to or slightly higher than those of the mDlx enhancer. Immunohistochemical analysis revealed that the mGAD65 promoter preferentially transduced parvalbumin (PV)-expressing interneurons. Notably, the mGAD65 promoter transduced chandelier cells more efficiently than the mDlx enhancer and robustly labeled their synaptic boutons, called the cartridge, targeting the axon initial segments of excitatory pyramidal neurons. To test the ability of the mGAD65 promoter to express a functional molecule, we virally expressed G-CaMP, a fluorescent Ca2+ indicator, in the motor cortex, and this enabled us to monitor spontaneous and drug-induced Ca2+ activity in GABAergic inhibitory neurons. These results suggest that the mGAD65 promoter is useful for AAV-mediated targeting and manipulation of GABAergic neurons with the dominance of cortical PV-expressing neurons, including chandelier cells.

scholarly journals Different inhibitory interneuron cell classes make distinct contributions to visual perception

2018 ◽  
Author(s):  
Jackson J. Cone ◽  
Megan D. Scantlen ◽  
Mark H. Histed ◽  
John H.R. Maunsell
Keyword(s):  
Visual Stimulation ◽  
Inhibitory Neuron ◽  
Inhibitory Interneuron ◽  
Neuron Activity ◽  
Improve Performance ◽  
Sensory Stimuli ◽  
Optogenetic Stimulation ◽  
Visual Contrast ◽  
Cortical Responses ◽  
Contrast Perception

SummaryWhile recent work has revealed how different inhibitory interneurons influence cortical responses to sensory stimuli, little is known about how their activity contributes to sensory perception. Here, we optogenetically stimulated different genetically defined interneurons (parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP)) in visual cortex (V1) of mice working at threshold in contrast increment or decrement detection tasks. The visual stimulus was paired with optogenetic stimulation to assess how enhancing V1 inhibitory neuron activity synchronously during cortical responses altered task performance. PV or SST activation impaired, while VIP stimulation improved, contrast increment detection. Notably, PV or SST stimulation also impaired contrast decrement detection, when opsin-evoked inhibition would exaggerate stimulus-evoked decrements in firing rate, and thus might improve performance. The impairment produced by PV or SST stimulation persisted throughout many weeks of testing. In contrast mice learned to reliably detect VIP activation in the absence of natural visual stimulation. Thus, different inhibitory signals make distinct contributions to visual contrast perception.

scholarly journals Twin-peak temporal regulation during human neocortical development

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Wei Wang ◽  
Guang-Zhong Wang
Keyword(s):  
Expression Patterns ◽  
Inhibitory Neuron ◽  
Perinatal Period ◽  
Inhibitory Neurons ◽  
Temporal Regulation ◽  
Twin Peaks ◽  
Neocortical Development ◽  
Temporal And Spatial ◽  
Hourglass Model ◽  
Second Peak

AbstractUnderstanding the temporal and spatial expression patterns of the human cerebral cortex is essential for expanding knowledge of its functionality. Previous analysis focused on the differentially expressed genes (DEGs) among cortical subregions revealed an hourglass model for interareal differences. However, the overall pattern of transcriptional differences during the development of every region remains to be fully explored. Here, analysing more than 800 neocortex samples from lifespan transcriptional profiles revealed that excitatory neurons are more regulated than inhibitory neurons in the foetal brain. Developmental DEGs tend to be resting state or memory encoding-related and are also involved in autism and Alzheimer’s disease. In addition, twin peaks of DEGs occur during the development of each neocortex region, with a first peak appearing in the perinatal period and an unexpected second peak appearing around childhood. Genes in these peaks have similar functions, but the second peak is more inhibitory neuron related. All these results emphasize the significance of this unique temporal regulatory pattern for human neocortical development.

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