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Magdalena Martinez-Losa, Tara E Tracy, Keran Ma, Laure Verret, Alexandra Clemente-Perez, Abdullah S Khan, Inma Cobos, Kaitlyn Ho, Li Gan, Lennart Mucke, Manuel Alvarez-Dolado, Jorge J Palop
Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD...
March 15, 2018: Neuron
Allie J Widman, Lori L McMahon
Low-dose ketamine, an open-channel N -methyl d-aspartate receptor (NMDAR) antagonist, mediates rapid antidepressant effects in humans that are mimicked in preclinical rodent models. Disinhibition of pyramidal cells via decreased output of fast-spiking GABAergic interneurons has been proposed as a key mechanism that triggers the antidepressant response. Unfortunately, to date, disinhibition has not been directly demonstrated. Furthermore, whether disinhibition is a common mechanism shared among other antagonists with rapid antidepressant properties in humans has not been investigated...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
J Stedehouder, D Brizee, G Shpak, S A Kushner
Axonal myelination of neocortical pyramidal neurons is dynamically modulated by neuronal activity. Recent studies have shown that a substantial proportion of neocortical myelin content is contributed by fast-spiking, parvalbumin (PV)-positive interneurons. However, it remains unknown whether the myelination of PV+ interneurons is also modulated by intrinsic activity. Here, we utilized cell-type specific Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in adult male and female mice to activate a sparse population of medial prefrontal cortex PV+ interneurons...
March 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Wei Cao, Shen Lin, Qiang-Qiang Xia, Yong-Lan Du, Qian Yang, Meng-Ying Zhang, Yi-Qing Lu, Jing Xu, Shu-Min Duan, Xia Jun, Guoping Feng, Junyu Xu, Jian-Hong Luo
Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice...
February 22, 2018: Neuron
Luke Joseph Bogart, Patricio O'Donnell
Several aspects of schizophrenia can be mimicked acutely in healthy human volunteers via administration of NMDA glutamate receptor (NMDAR) antagonists. As these agents decrease firing rates in prefrontal cortical (PFC) GABAergic fast-spiking interneurons (FSI) in animal studies, a leading hypothesis on schizophrenia pathophysiology is that NMDAR in FSI are impaired. However, whole-cell recordings of FSI in slices of adult mouse PFC revealed limited amounts of NMDAR-mediated current. Since those studies used local electrical stimulation to activate a heterogeneous set of synaptic inputs to the recorded cell, it is unclear whether specific afferent inputs may preferentially drive NMDAR responses in FSI...
February 26, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Maxime Assous, James M Tepper
The striatum constitutes the main input structure of the basal ganglia and receives two major excitatory glutamatergic inputs, from the cortex and the thalamus. Excitatory cortico- and thalamo-striatal connections innervate the principal neurons of the striatum, the spiny projection neurons (SPNs), which constitute the main cellular input as well as the only output of the striatum. In addition, corticostriatal and thalamostriatal inputs also innervate striatal interneurons. Some of these inputs have been very well studied, e...
February 26, 2018: European Journal of Neuroscience
Nuné Martiros, Alexandra A Burgess, Ann M Graybiel
Understanding neural representations of behavioral routines is critical for understanding complex behavior in health and disease. We demonstrate here that accentuated activity of striatal projection neurons (SPNs) at the beginning and end of such behavioral repertoires is a supraordinate representation specifically marking previously rewarded behavioral sequences independent of the individual movements making up the behavior. We recorded spike activity in the striatum and primary motor cortex as individual rats learned specific rewarded lever-press sequences, each one unique to a given rat...
February 1, 2018: Current Biology: CB
Scott F Owen, Joshua D Berke, Anatol C Kreitzer
Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrophysiology, imaging, and behavior to describe a unified mechanism by which striatal FSIs control burst firing, calcium influx, and synaptic plasticity in neighboring medium spiny projection neurons (MSNs)...
February 8, 2018: Cell
Gabriel Koch Ocker, Brent Doiron
The synaptic connectivity of cortex is plastic, with experience shaping the ongoing interactions between neurons. Theoretical studies of spike timing-dependent plasticity (STDP) have focused on either just pairs of neurons or large-scale simulations. A simple analytic account for how fast spike time correlations affect both microscopic and macroscopic network structure is lacking. We develop a low-dimensional mean field theory for STDP in recurrent networks and show the emergence of assemblies of strongly coupled neurons with shared stimulus preferences...
February 3, 2018: Cerebral Cortex
Hiroki Toyoda
Nicotinic acetylcholine receptors (nAChRs) in the insular cortex play an important role in nicotine addiction, but its cellular and synaptic mechanisms underlying nicotine addiction still remain unresolved. In layer 5 pyramidal neurons of the mouse insular cortex, activation of nAChRs suppresses synaptic potentiation through enhancing GABAergic synaptic transmission via activation of β2-containing nAChRs in non-fast-spiking (non-FS) interneurons. However, it has not been addressed whether and how activation of nAChRs modulates synaptic plasticity in layer 3 and 6 pyramidal neurons of the insular cortex...
February 6, 2018: European Journal of Neuroscience
L Guarina, C Calorio, D Gavello, E Moreva, P Traina, A Battiato, S Ditalia Tchernij, J Forneris, M Gai, F Picollo, P Olivero, M Genovese, E Carbone, A Marcantoni, V Carabelli
Fluorescent nanodiamonds (FND) are carbon-based nanomaterials that can efficiently incorporate optically active photoluminescent centers such as the nitrogen-vacancy complex, thus making them promising candidates as optical biolabels and drug-delivery agents. FNDs exhibit bright fluorescence without photobleaching combined with high uptake rate and low cytotoxicity. Focusing on FNDs interference with neuronal function, here we examined their effect on cultured hippocampal neurons, monitoring the whole network development as well as the electrophysiological properties of single neurons...
February 2, 2018: Scientific Reports
Jing Ye, Menno P Witter, May-Britt Moser, Edvard I Moser
The mammalian positioning system contains a variety of functionally specialized cells in the medial entorhinal cortex (MEC) and the hippocampus. In order for cells in these systems to dynamically update representations in a way that reflects ongoing movement in the environment, they must be able to read out the current speed of the animal. Speed is encoded by speed-responsive cells in both MEC and hippocampus, but the relationship between the two populations has not been determined. We show here that many entorhinal speed cells are fast-spiking putative GABAergic neurons...
January 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
Lixia Gao, Xiaoqin Wang
Extracellular recording studies have revealed diverse and selective neural responses in the primary auditory cortex (A1) of awake animals. However, we have limited knowledge on subthreshold events that give rise to these responses, especially in non-human primates, as intracellular recordings in awake animals pose substantial technical challenges. We developed a novel intracellular recording technique in awake marmosets to systematically study subthreshold activity of A1 neurons that underlies their diverse and selective spiking responses...
January 25, 2018: Cerebral Cortex
Kyuhyun Choi, Elizabeth Holly, M Felicia Davatolhagh, Kevin T Beier, Marc V Fuccillo
The dorsomedial striatum, a key site of reward-sensitive motor output, receives extensive afferent input from cortex, thalamus and midbrain. These projections are integrated by striatal microcircuits containing both spiny projection neurons and local circuit interneurons. To explore target-cell specificity of these projections, we compared inputs onto D1-dopamine receptor positive spiny neurons, parvalbumin-positive fast-spiking interneurons and somatostatin-positive low-threshold-spiking interneurons, using cell-type specific rabies virus tracing and optogenetic-mediated projection neuron recruitment in mice...
January 23, 2018: European Journal of Neuroscience
Nouk Tanke, J Gerard G Borst, Arthur R Houweling
A single whisker stimulus elicits action potentials in a sparse subset of neurons in somatosensory cortex. The precise contribution of these neurons to the animal's perception of a whisker stimulus is unknown. Here we show that single-cell stimulation in rat barrel cortex of both sexes influences the psychophysical detection of a near-threshold whisker stimulus in a cell type-dependent manner, without affecting false alarm rate. Counterintuitively, stimulation of single fast-spiking putative inhibitory neurons increased detection performance...
January 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Joshua Nichols, George Reed Bjorklund, Jason Newbern, Trent Anderson
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Traditionally, ongoing neurodevelopment and neuroplasticity have thought to confer children with an advantage following TBI. However, recent findings indicate that the pediatric brain may be more sensitive to brain injury. Inhibitory interneurons are essential for proper cortical function and implicated in the pathophysiology of TBI, yet few studies have directly examined for TBI induced changes to interneurons themselves...
January 15, 2018: Journal of Physiology
Yael Oran, Izhar Bar-Gad
Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats before and after selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum...
February 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Vishalini Emmenegger, Guanxiao Qi, Haijun Wang, Dirk Feldmeyer
GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons,2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons,4) intra-columnar projecting VIP-like interneurons,and5) locally projecting neurogliaform-like interneurons...
January 10, 2018: Cerebral Cortex
Maximiliano José Nigro, Yoshiko Hashikawa-Yamasaki, Bernardo Rudy
Inhibitory interneurons represent 10-15% of the neurons in the somatosensory cortex, and their activity powerfully shapes sensory processing. Three major groups of GABAergic interneurons have been defined according to developmental, molecular, morphological, electrophysiological, and synaptic features. Dendritic-targeting somatostatin-expressing interneurons (SST-INs) have been shown to display diverse morphological, electrophysiological, and molecular properties and activity patterns in vivo However, the correlation between these properties and SST-IN subtype is unclear...
February 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Si-Qiang Ren, Wen Yao, Jing-Zhi Yan, Chunhui Jin, Jia-Jun Yin, Jianmin Yuan, Shui Yu, Zaohuo Cheng
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. At the early stages of AD development, the soluble β-amyloid (Aβ) induces synaptic dysfunction, perturbs the excitation/inhibition balance of neural circuitries, and in turn alters the normal neural network activity leading to cognitive decline, but the underlying mechanisms are not well established. Here by using whole-cell recordings in acute mouse brain slices, we found that 50 nM Aβ induces hyperexcitability of excitatory pyramidal cells in the cingulate cortex, one of the most vulnerable areas in AD, via depressing inhibitory synaptic transmission...
January 10, 2018: Scientific Reports
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