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interneuron plasticity

Lhotse Hei Lui Ng, Yuhua Huang, Lei Han, Raymond Chuen-Chung Chang, Ying Shing Chan, Cora Sau Wan Lai
Stress is a major risk factor for the onset of many psychiatric diseases. In rodent models, chronic stress induces depression and impairs excitatory neurotransmission. However, little is known about the effect of stress on synaptic circuitry during the development of behavioral symptoms. Using two-photon transcranial imaging, we studied the effect of repeated restraint stress on dendritic spine plasticity in the frontal cortex in vivo. We found that restraint stress induced dendritic spine loss by decreasing the rate of spine formation and increasing the rate of spine elimination...
December 10, 2018: Translational Psychiatry
Nichola Marie Brydges, Anna Moon, Lowenna Rule, Holly Watkin, Kerrie L Thomas, Jeremy Hall
Experience of traumatic events in childhood is linked to an elevated risk of developing psychiatric disorders in adulthood. The neurobiological mechanisms underlying this phenomenon are not fully understood. The limbic system, particularly the hippocampus, is significantly impacted by childhood trauma. In particular, it has been hypothesised that childhood stress may impact adult hippocampal neurogenesis (AHN) and related behaviours, conferring increased risk for later mental illness. Stress in utero can lead to impaired hippocampal synaptic plasticity, and stress in the first 2-3 weeks of life reduces AHN in animal models...
December 10, 2018: Translational Psychiatry
Simon Chamberland, Alfonsa Zamora Moratalla, Lisa Topolnik
Local circuit GABAergic inhibitory interneurons control the integration and transfer of information in many brain regions. Several different forms of plasticity reported at interneuron excitatory synapses are triggered by cell- and synapse-specific postsynaptic calcium (Ca2+ ) mechanisms. To support this function, the spatiotemporal dynamics of dendritic Ca2+ elevations must be tightly regulated. While the dynamics of postsynaptic Ca2+ signaling through activation of different Ca2+ sources has been explored, the Ca2+ extrusion mechanisms that operate in interneuron dendrites during different patterns of activity remain largely unknown...
December 4, 2018: Cell Calcium
Clémentine Quintana, Jean-Martin Beaulieu
The dopamine D2 receptor (DRD2) remains the principal target of antipsychotic drugs used for the management of schizophrenia and other psychotic disorders. This receptor is highly expressed within the basal ganglia, more specifically the striatal caudate nucleus and the nucleus accumbens. The general functions, signaling and behavioral contributions of striatal DRD2 are well understood. However, the study of cortical DRD2 expression and functions has for the most part been restricted to a subset of pyramidal neurons and interneurons (e...
December 4, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Elise Magnin, Ruggiero Francavilla, Sona Amalyan, Etienne Gervais, Linda Suzanne David, Xiao Luo, Lisa Topolnik
Hippocampus-dependent learning processes are coordinated via a large diversity of GABAergic inhibitory mechanisms. The alpha5 subunit-containing GABAA receptor (α5-GABAA R) is abundantly expressed in the hippocampus populating primarily the extrasynaptic domain of CA1 pyramidal cells, where it mediates tonic inhibitory conductance and may cause functional deficits in synaptic plasticity and hippocampus-dependent memory. However, little is known about synaptic expression of the α5-GABAA R and, accordingly, its location site-specific function...
December 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Enhui Pan, Zirun Zhao, James O McNamara
Hippocampal mossy fiber axons simultaneously activate CA3 pyramidal cells and stratum lucidum interneurons (SLIN), the latter providing feedforward inhibition to control CA3 pyramidal cell excitability. Filopodial extensions of giant boutons of mossy fibers provide excitatory synaptic input to the SLIN. These filopodia undergo extraordinary structural plasticity causally linked to executing memory tasks, leading us to seek the mechanisms by which activity regulates these synapses. High frequency stimulation of the mossy fibers induces LTD of their calcium permeable-AMPA receptor synapses with SLINs; previous work localized site of induction to be postsynaptic and site of expression to be presynaptic...
December 5, 2018: Journal of Neurophysiology
Hongsheng Wang, Fang Liu, Wenbing Chen, Xiangdong Sun, Wanpeng Cui, Zhaoqi Dong, Kai Zhao, Hongsheng Zhang, Haiwen Li, Guanglin Xing, Erkang Fei, Bing-Xing Pan, Bao-Ming Li, Wen-Cheng Xiong, Lin Mei
Neurotrophic factor NRG1 and its receptor ErbB4 play a role in GABAergic circuit assembly during development. ErbB4 null mice possess fewer interneurons, have decreased GABA release, and show impaired behavior in various paradigms. In addition, NRG1 and ErbB4 have also been implicated in regulating GABAergic transmission and plasticity in matured brains. However, current ErbB4 mutant strains are unable to determine whether phenotypes in adult mutant mice result from abnormal neural development. This important question, a glaring gap in understanding NRG1-ErbB4 function, was addressed by using two strains of mice with temporal control of ErbB4 deletion and expression, respectively...
November 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
Juan F Ramirez-Villegas, Konstantin F Willeke, Nikos K Logothetis, Michel Besserve
Hippocampal ripple oscillations likely support reactivation of memory traces that manifest themselves as temporally organized spiking of sparse neuronal ensembles. However, the network mechanisms concurring to achieve this function are largely unknown. We designed a multi-compartmental model of the CA3-CA1 subfields to generate biophysically realistic ripple dynamics from the cellular level to local field potentials. Simulations broadly parallel in vivo observations and support that ripples emerge from CA1 pyramidal spiking paced by recurrent inhibition...
October 23, 2018: Neuron
Leena E Williams, Anthony Holtmaat
Sensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons (PNs), largely mediated by synaptic long-term potentiation (LTP). The circuit mechanisms underlying cortical LTP remain unclear. In the mouse somatosensory cortex, LTP can be elicited in layer 2/3 PNs by rhythmic whisker stimulation. We dissected the synaptic circuitry underlying this type of plasticity in thalamocortical slices. We found that projections from higher-order, posterior medial thalamic complex (POm) are key to eliciting N-methyl-D-aspartate receptor (NMDAR)-dependent LTP of intracortical synapses...
November 16, 2018: Neuron
Chun-Wai Ma, Pui-Yi Kwan, Kenneth Lap-Kei Wu, Daisy Kwok-Yan Shum, Ying-Shing Chan
Perineuronal nets (PN) restrict neuronal plasticity in the adult brain. We hypothesize that activity-dependent consolidation of PN is required for functional maturation of behavioral circuits. Using the postnatal maturation of brainstem vestibular nucleus (VN) circuits as a model system, we report a neonatal period in which consolidation of central vestibular circuitry for graviception is accompanied by activity-dependent consolidation of chondroitin sulfate (CS)-rich PN around GABAergic neurons in the VN. Postnatal onset of negative geotaxis was used as an indicator for functional maturation of vestibular circuits...
November 20, 2018: Brain Structure & Function
Zhanhong Zhou, Xiaolong Zhai, Chung Tin
Cerebellum possesses very rich motor control and learning capability which is critical for animals. In this study, we proposed a spiking neural network model of cerebellum for gain and phase adaptation in vestibulo-ocular reflex (VOR). VOR is a critical adaptive reflexive eye movement for maintaining a stable visual field. In this model (with neuron number at the order of 104), synaptic plasticity at parallel fiber-Purkinje cell synapses was considered. In particular, we have shown that the inhibitory inputs from molecular layer interneurons on Purkinje cells play a critical role in phase adaptation of VOR...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Katerina Kalemaki, Xanthippi Konstantoudaki, Simona Tivodar, Kyriaki Sidiropoulou, Domna Karagogeos
GABAergic (γ-aminobutyric acid) neurons are inhibitory neurons and protect neural tissue from excessive excitation. Cortical GABAergic neurons play a pivotal role for the generation of synchronized cortical network oscillations. Imbalance between excitatory and inhibitory mechanisms underlies many neuropsychiatric disorders and is correlated with abnormalities in oscillatory activity, especially in the gamma frequency range (30-80 Hz). We investigated the functional changes in cortical network activity in response to developmentally reduced inhibition in the adult mouse barrel cortex (BC)...
2018: Frontiers in Neural Circuits
Maya Kono, Wataru Kakegawa, Kazunari Yoshida, Michisuke Yuzaki
KEY POINTS: NMDA receptors (NMDARs) are required for long-term depression (LTD) at parallel fibre-Purkinje cell synapses, but their cellular localization and physiological functions in vivo are unclear. NMDARs in molecular-layer interneurons (MLIs), but not granule cells or Purkinje cells, are required for LTD, but not long-term potentiation induced by low-frequency stimulation of parallel fibres. Nitric oxide produced by NMDAR activation in MLIs probably mediates LTD induction. NMDARs in granule cells or Purkinje cells are dispensable for motor learning during adaptation of horizontal optokinetic responses...
November 1, 2018: Journal of Physiology
Maxime Lévesque, Massimo Avoli
Theta oscillations (4-12 Hz) represent one of the most prominent physiological oscillatory activity in the mammalian EEG. They are observed in several areas of the hippocampus and in parahippocampal structures. Theta oscillations play important roles in modulating synaptic plasticity during memory and learning; moreover, they are dependent on septal cholinergic inputs. Theta oscillations can be reproduced in vitro in several regions of the temporal lobe in the absence of the septum by employing the cholinergic agonist carbachol (CCh)...
October 28, 2018: Neuroscience and Biobehavioral Reviews
Txomin Lalanne, Julia Oyrer, Mark Farrant, P Jesper Sjöström
Calcium-permeable (CP) AMPA-type glutamate receptors (AMPARs) are known to mediate synaptic plasticity in several different interneuron (IN) types. Recent evidence suggests that CP-AMPARs are synapse-specifically expressed at excitatory connections onto a subset of IN types in hippocampus and neocortex. For example, CP-AMPARs are found at connections from pyramidal cells (PCs) to basket cells (BCs), but not to Martinotti cells (MCs). This synapse type-specific expression of CP-AMPARs suggests that synaptic dynamics as well as learning rules are differentially implemented in local circuits and has important implications not just in health but also in disease states such as epilepsy...
2018: Frontiers in Synaptic Neuroscience
Akiko Sakai, Sayaka Sugiyama
During brain development, once primary neural networks are formed, they are largely sculpted by environmental stimuli. The juvenile brain has a unique time window termed the critical period, in which neuronal circuits are remodeled by experience. Accumulating evidence indicates that abnormal rewiring of circuits in early life contributes to various neurodevelopmental disorders at later stages of life. Recent studies implicate two important aspects for activation of the critical period, both of which are experience-dependent: (a) proper excitatory/inhibitory (E/I) balance of neural circuit achieved during developmental trajectory of inhibitory interneurons, and (b) epigenetic regulation allowing flexible gene expression for neuronal plasticity...
October 2018: Development, Growth & Differentiation
Yuhua Yin, Min-Hee Yi, Dong Woon Kim
Neuropathic pain (NP) is caused by lesions of the peripheral fibers and central neurons in the somatosensory nervous system and affects 7-10% of the general population. Although the distinct cause of neuropathic pain has been investigated in primary afferent neurons over the years, pain modulation by central sensitization remains controversial. NP is believed to be driven by cell type-specific spinal synaptic plasticity in the dorsal horn. Upon intense afferent stimulation, spinothalamic tract neurons are potentiated, whereas GABAergic interneurons are inhibited leading to long-term depression...
2018: Pain Research & Management: the Journal of the Canadian Pain Society
Cristina Alba-Delgado, Sarah Mountadem, Noémie Mermet-Joret, Lénaïc Monconduit, Radhouane Dallel, Alain Artola, Myriam Antri
Mechanical allodynia, a widespread pain symptom which still lacks effective therapy, is associated with the activation of a dorsally-directed polysynaptic circuit within spinal (SDH) or medullary dorsal horn (MDH), whereby tactile inputs into deep SDH/MDH can gain access to superficial SDH/MDH, eliciting pain. Inner lamina II (IIi ) interneurons expressing the γ isoform of protein kinase C (PKCγ+ ) are key elements for allodynia circuits but how they operate is still unclear. Combining behavioral, ex vivo electrophysiological and morphological approaches in an adult rat model of facial inflammatory pain (Complete Freund's Adjuvant, CFA), we show that the mechanical allodynia observed 1h after CFA injection is associated with i) sensitization (using ERK1/2 phosphorylation as a marker) and ii) reduced dendritic arborizations and enhanced spine density-in exclusively PKCγ+ interneurons, but iii) depolarized resting membrane potential (RMP) in all lamina IIi PKCγ+ /PKCγ- interneurons...
October 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lei Zhong, Xin Chen, Esther Park, Thomas C Südhof, Lu Chen
Homeostatic synaptic plasticity is a synaptic mechanism through which the nervous system adjusts synaptic excitation and inhibition to maintain network stability. Retinoic acid (RA) and its receptor RARα have been established as critical mediators of homeostatic synaptic plasticity. In vitro studies reveal that RA signaling enhances excitatory synaptic strength and decreases inhibitory synaptic strength. However, it is unclear whether RA-mediated homeostatic synaptic plasticity occurs in vivo , and if so, whether it operates at specific types of synapses...
October 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lisa Topolnik, Olivier Camiré
Understanding of how intracellular calcium (Ca2+ ) signals regulate the efficacy of transmission at excitatory and inhibitory synapses in the central nervous system (CNS) has been a focus of intense investigation. This review discusses recent findings on how Ca2+ signals are integrated in dendrites of inhibitory interneurons to regulate their synapses. In particular, Ca2+ signaling through intracellular Ca2+ release plays an essential role in synaptic signal transduction and experience-dependent plasticity in dendrites of interneurons...
October 12, 2018: Current Opinion in Neurobiology
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