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Ewa Siucinska, Wojciech Brutkowski, Tytus Bernas
We found previously that fear conditioning by combined stimulation of a row B facial vibrissae (conditioned stimulus, CS) with a tail shock (unconditioned stimulus, UCS) leads to expansion of the cortical representation of the "trained" row, labeled with 2-deoxyglucose (2DG), in the layer IIIb/IV of the adult mouse the primary somatosensory cortex (S1) 24 h later. We have observed that learning - dependent these plastic changes are manifested by increased expression of somatostatin, cholecystokinin (SST+, CCK+) but not parvalbumin (PV+) immunopositive interneurons...
March 14, 2018: ACS Chemical Neuroscience
Juan R Martinez-Galan, Ana Verdejo, Elena Caminos
Disturbances in calcium homeostasis due to canonical transient receptor potential (TRPC) and/or store-operated calcium (SOC) channels can play a key role in a large number of brain disorders. TRPC channels are plasma membrane cation channels included in the transient receptor potential (TRP) superfamily. The most widely distributed member of the TRPC subfamily in the brain is TRPC1, which is frequently linked to group I metabotropic glutamate receptors (mGluRs) and to the components of SOC channels. Proposing TRPC/SOC channels as a therapeutic target in neurological diseases previously requires a detailed knowledge of the distribution of such molecules in the brain...
2018: Frontiers in Neuroanatomy
P Lorenzo Bozzelli, Seham Alaiyed, Eunyoung Kim, Sonia Villapol, Katherine Conant
The perineuronal net (PNN) represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV-) positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples...
2018: Neural Plasticity
Eugenia Tomasella, Lucila Bechelli, Mora Belén Ogando, Camilo Mininni, Mariano N Di Guilmi, Fernanda De Fino, Silvano Zanutto, Ana Belén Elgoyhen, Antonia Marin-Burgin, Diego M Gelman
Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alexander J Riordan, Ari W Schaler, Jenny Fried, Tracie A Paine, Janice E Thornton
The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP...
February 27, 2018: Psychoneuroendocrinology
Nannan Guo, Marta E Soden, Charlotte Herber, Michael TaeWoo Kim, Antoine Besnard, Paoyan Lin, Xiang Ma, Constance L Cepko, Larry S Zweifel, Amar Sahay
Memories become less precise and generalized over time as memory traces reorganize in hippocampal-cortical networks. Increased time-dependent loss of memory precision is characterized by an overgeneralization of fear in individuals with post-traumatic stress disorder (PTSD) or age-related cognitive impairments. In the hippocampal dentate gyrus (DG), memories are thought to be encoded by so-called 'engram-bearing' dentate granule cells (eDGCs). Here we show, using rodents, that contextual fear conditioning increases connectivity between eDGCs and inhibitory interneurons (INs) in the downstream hippocampal CA3 region...
March 12, 2018: Nature Medicine
Diego E Pafundo, Takeaki Miyamae, David A Lewis, Guillermo Gonzalez-Burgos
BACKGROUND: Testing hypotheses regarding the role of N-methyl-D-aspartate receptor (NMDAR) hypofunction in schizophrenia requires understanding the mechanisms of NMDAR regulation of prefrontal cortex (PFC) circuit function. NMDAR antagonists are thought to produce pyramidal cell (PC) disinhibition. However, inhibitory parvalbumin-positive basket cells (PVBCs) have modest NMDAR-mediated excitatory drive and thus are unlikely to participate in NMDAR antagonist-mediated disinhibition. Interestingly, recent studies demonstrated that presynaptic NMDARs enhance transmitter release at central synapses...
January 31, 2018: Biological Psychiatry
Danny Jazmati, Ute Neubacher, Klaus Funke
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is able to modify cortical excitability. Rat rTMS studies revealed a modulation of inhibitory systems, in particular that of the parvalbumin-expressing (PV+) interneurons, when using intermittent theta-burst stimulation (iTBS). OBJECTIVE: The potential disinhibitory action of iTBS raises the questions of how neocortical circuits stabilize excitatory-inhibitory balance within a physiological range. Neuropeptide Y (NPY) appears to be one candidate...
February 24, 2018: Brain Stimulation
Masayoshi Kurachi, Tsutomu Takahashi, Tomiki Sumiyoshi, Takashi Uehara, Michio Suzuki
Background: A recent review reported that the median proportion of patients recovering from schizophrenia was 13.5% and that this did not change over time. Various factors including the duration of untreated psychosis, cognitive impairment, negative symptoms, and morphological changes in the brain influence the functional outcome of schizophrenia. The authors herein reviewed morphological changes in the brain of schizophrenia patients, effects of early intervention, and a direction of developing novel therapeutics to achieve significant improvement of the functional outcome...
2018: Frontiers in Psychiatry
Christian Mayer, Christoph Hafemeister, Rachel C Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell, Rahul Satija
Diverse subsets of cortical interneurons have vital roles in higher-order brain functions. To investigate how this diversity is generated, here we used single-cell RNA sequencing to profile the transcriptomes of mouse cells collected along a developmental time course. Heterogeneity within mitotic progenitors in the ganglionic eminences is driven by a highly conserved maturation trajectory, alongside eminence-specific transcription factor expression that seeds the emergence of later diversity. Upon becoming postmitotic, progenitors diverge and differentiate into transcriptionally distinct states, including an interneuron precursor state...
March 5, 2018: Nature
Rong-Jun Ni, Zhao-Huan Huang, Yu-Mian Shu, Yu Wang, Tao Li, Jiang-Ning Zhou
The striatum and globus pallidus are principal nuclei of the basal ganglia. Nissl- and acetylcholinesterase-stained sections of the tree shrew brain showed the neuroanatomical features of the caudate nucleus (Cd), internal capsule (ic), putamen (Pu), accumbens, internal globus pallidus, and external globus pallidus. The ic separated the dorsal striatum into the Cd and Pu in the tree shrew, but not in rats and mice. In addition, computer-based 3D images allowed a better understanding of the position and orientation of these structures...
March 5, 2018: Neuroscience Bulletin
Federica Filice, Emanuel Lauber, Karl Jakob Vörckel, Markus Wöhr, Beat Schwaller
Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by two core symptoms: impaired social interaction and communication, and restricted, repetitive behaviors and interests. The pathophysiology of ASD is not yet fully understood, due to a plethora of genetic and environmental risk factors that might be associated with or causal for ASD. Recent findings suggest that one putative convergent pathway for some forms of ASD might be the downregulation of the calcium-binding protein parvalbumin (PV)...
2018: Molecular Autism
Weiguo Yang, Qian-Quan Sun
We used ChR2-assisted circuit mapping (CRACM) to examine neuronal/compartmental excitatory and inhibitory synaptic balance (E-I balance) in pyramidal cells (PCs) located in several brain regions (including both neocortices and paleocortices). Within the vS1, different inputs on the same neurons, or the same inputs formed on different targets, induced different E/I ratios. E/I ratios in PCs from different regions were largely different. Chemogenetic silencing of somatostatin (SOM)- or parvalbumin (PV)-containing interneurons (INs) while optogenetically activating long-range M1 inputs demonstrated differential contribution of PV and SOM INs to the E/I ratios in a layer-specific manner in S1...
March 5, 2018: Scientific Reports
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
Jianjun Zhu, Mingpeng Jin, Jiaojiao Wang, Hui Zhang, Yousheng Wu, Deyang Li, Xiaoying Ji, Hushan Yang, Chun Yin, Tingting Ren, Jinliang Xing
BACKGROUND: Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved. METHODS: The level of cytosolic Ca2+ was assessed by Fura-2 in HCC cells. After changing cytosolic Ca2+ level by using agonists or inhibitors, cell apoptosis was detected by flow cytometry...
March 5, 2018: Journal of Experimental & Clinical Cancer Research: CR
P A Zykin, I A Moiseenko, L A Tkachenko, R A Nasyrov, E A Tsvetkov, E I Krasnoshchekova
We studied peculiarities of the structure of human entorhinal cortex at weeks 20-26 of gestation (10 hemispheres). The samples were Nissl-stained and immunohistochemically treated with antibodies to parvalbumin, calretinin, calbindin, and cytoskeleton proteins (MAP2 and N200). 3D-reconstruction of the entorhinal cortex from serial sections was performed, caudomedial and rostrolateral areas were isolated. Parvalbumin+ cells in layer I, discrete distribution of layer II cells with colocalization of MAP2 and calretinin at the border with layer I, and two sublayers Va and Vb with MAP2+ neurons were typical for the caudomedial area...
March 4, 2018: Bulletin of Experimental Biology and Medicine
Kenneth N Fish, Brad R Rocco, David A Lewis
In human prefrontal cortex (PFC), ~85% of γ-aminobutyric acid (GABA)-expressing neurons can be subdivided into non-overlapping groups by the presence of calbindin (CB), calretinin (CR) or parvalbumin (PV). Substantial research has focused on the differences in the laminar locations of the cells bodies of these neurons, with limited attention to the distribution of their axon terminals, their sites of action. We previously reported that in non-human primates subtypes of these cells are distinguishable by differences in terminal protein levels of the GABA synthesizing enzymes glutamic acid decarboxylase 65 (GAD65) and GAD67...
2018: Frontiers in Neuroanatomy
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
Alexandra K Moore, Aldis P Weible, Timothy S Balmer, Laurence O Trussell, Michael Wehr
Excitation is balanced by inhibition to cortical neurons across a wide range of conditions. To understand how this relationship is maintained, we broadly suppressed the activity of parvalbumin-expressing (PV+ ) inhibitory neurons and asked how this affected the balance of excitation and inhibition throughout auditory cortex. Activating archaerhodopsin in PV+ neurons effectively suppressed them in layer 4. However, the resulting increase in excitation outweighed Arch suppression and produced a net increase in PV+  activity in downstream layers...
February 16, 2018: Neuron
Jill R Glausier, David A Lewis
Schizophrenia is a complex disorder lacking an effective treatment option for the pervasive and debilitating cognitive impairments experienced by patients. Working memory is a core cognitive function impaired in schizophrenia that depends upon activation of distributed neural network, including the circuitry of the dorsolateral prefrontal cortex (DLPFC). Accordingly, individuals diagnosed with schizophrenia show reduced DLPFC activation while performing working-memory tasks. This lower DLPFC activation appears to be an integral part of the disease pathophysiology, and not simply a reflection of poor performance...
2018: Handbook of Clinical Neurology
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