Autapses selectively form in specific cell types in many brain regions. Previous studies have also found putative autapses in principal spiny projection neurons (SPNs) in the striatum. However, it remains unclear whether these neurons indeed form physiologically functional autapses. We applied whole-cell recording in striatal slices and identified autaptic cells by the occurrence of prolonged asynchronous release (AR) of neurotransmitters after bursts of high-frequency action potentials (APs). Surprisingly, we found no autaptic AR in SPNs, even in the presence of Sr²⁺. However, robust autaptic AR was recorded in parvalbumin (PV)-expressing neurons. The autaptic responses were mediated by GABA_A receptors and their strength was dependent on AP frequency and number. Further computer simulations suggest that autapses regulate spiking activity in PV cells by providing self-inhibition and thus shape network oscillations. Together, our results indicate that PV neurons, but not SPNs, form functional autapses, which may play important roles in striatal functions.
Parvalbumins/metabolism* ; Corpus Striatum/metabolism* ; Interneurons/physiology* ; Neurons/metabolism* ; Neostriatum

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a
Animals ; Interneurons/metabolism* ; Mice ; Neurons/metabolism* ; Parvalbumins/metabolism* ; Receptors, Serotonin, 5-HT3/genetics* ; Serotonin ; Somatostatin/metabolism*

This study aims to explore the electrophysiological properties and changes in gene expression of basket cells, a unique population of GABAergic interneurons expressing parvalbumin (PV), during the postnatal development of mouse prefrontal cortex (PFC). Toward this goal, we took use of the G42 transgenic mouse line which specifically expresses enhanced green fluorescent protein (EGFP) in basket cells. The brain slices of PFC were prepared from the postnatal 7 (P7), 14 (P14) and 21 days (P42) G42 mice and whole-cell patch clamp recording was performed in basket cells. In addition, we sorted the basket cells by flow cytometry and analyzed their transcription profiling on P7, P14, and P21 using RNA-seq technology. The results showed that the resting membrane potential and membrane input resistance decreased gradually from P7 to P21. The amplitude and duration of action potential of basket cells increased and decreased from P7 to P21, respectively. In contrast, the threshold of action potential of basket cells did not have a significant change from P7 to P21. The frequency of spontaneous excitatory postsynaptic currents (sEPSCs) of basket cells increased gradually, while the amplitudes of sEPSCs of basket cells remained constant from P7 to P21. RNA sequencing from basket cells revealed that the expression of 22 and 660 genes was upregulated and downregulated from P7 to P14, respectively. By contrast, the expression of 107 and 69 genes was upregulated and downregulated from P14 to P21, respectively. The differentially expressed genes in basket cells from P7 to P21 were significantly enriched in pathways such as neuron apoptotic process, mRNA processing, Golgi vesicle transport and axon guidance. Altogether, we characterized electrophysiological properties and changes in gene expression of basket cells during the postnatal development in mouse PFC. These results provide insight into the mechanisms underlying the development of basket cells in mouse cortex.
Animals ; Gene Expression ; Interneurons/metabolism* ; Mice ; Mice, Transgenic ; Parvalbumins/metabolism* ; Prefrontal Cortex/metabolism*

The α2A adrenoceptors (α2A-ARs) are the most common adrenergic receptor subtype found in the prefrontal cortex (PFC). It is generally accepted that stimulation of postsynaptic α2A-ARs on pyramidal neurons are key to PFC functions, such as working memory. However, the expression of α2A-ARs in interneurons is largely unknown. In the present study using double-labeling immunofluorencence technique, we investigated the expression of α2A-ARs in major types of rat PFC interneurons expressing calcium-binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). Our data demonstrated that α2A-ARs are highly expressed in calcium-binding protein immunoreactive interneurons of rat PFC, suggesting that stimulation of α2A-ARs may alter neural networks comprising pyramidal neurons and interneurons, thereby exerting a beneficial effect on PFC cognitive functions. The present study provides the morphological basis for a potential mechanism by which stimulation of α2A-ARs induces cognitive improvement.
Animals ; Calbindin 2 ; metabolism ; Calbindins ; metabolism ; Interneurons ; metabolism ; Parvalbumins ; metabolism ; Prefrontal Cortex ; cytology ; Rats ; Receptors, Adrenergic, alpha-2 ; metabolism

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N
Animals ; Interneurons/metabolism* ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins/metabolism* ; Neurons/metabolism* ; Nucleus Accumbens/metabolism* ; Parvalbumins/metabolism*

The purpose of this study was to identify specific microRNAs (miRNAs) during differentiation and maturation of interneurons and to predict their possible functions by analyzing the expression of miRNAs during in vitro differentiation of the rat interneuron precursor cell line GE6. In the experiment, the interneuron precursor cell line GE6 was cultured under three different conditions, i. e. the first was that had not added growth factors and the normal differentiation cultured for 4 days (Ge6_4d); the second was that cultured with bone morphogenetic protein-2 (BMP2) for 4 days (Ge6_bmp2); and the third was that cultured with sonic hedgehog (SHH) for 4 days (Ge6_ shh). In addition, another group of undifferentiated GE6 (Ge6_u) was applied as a control. We found in this study that the expression levels of a large number of miRNAs changed significantly during GE6 differentiation. The expression levels of miR-710, miR-290-5p and miR-3473 increased in the GE6 cells with secreted factor BMP2. These miRNAs may play important regulatory roles during interneuron differentiation.
Animals ; Bone Morphogenetic Protein 2 ; chemistry ; Cell Differentiation ; Cell Line ; Hedgehog Proteins ; chemistry ; Interneurons ; cytology ; metabolism ; MicroRNAs ; metabolism ; Rats

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.
Autism Spectrum Disorder/metabolism* ; Cell Movement/genetics* ; Humans ; Interneurons/metabolism* ; Neurodevelopmental Disorders/genetics* ; Neurons/metabolism* ; Rho Guanine Nucleotide Exchange Factors/genetics*

OBJECTIVETo generate mice which are specific for peroxisomproliferator-activated receptor-γ coactivator-1(PGC-1α) knockout in the GABAergic interneuron.

METHODSConditional mice specific for PGC-1αwere introduced from the Jackson Laboratory, USA and initially inbred to obtain homozygote PGC-1αmice. The PGC-1αconditional mice were further crossed with Dlx5/6-Cre-IRES-EGFP transgenic mice to achieve specific knockout of PGC-1α in the GABAergic interneuron.

RESULTSThe offspring with specific knockout PGC-1α gene were successful for the generation of GABAergic interneuron, with the resulting genotype being PGC-1α.

CONCLUSIONThe PGC-1αmice were obtained through a proper crossing strategy, which has provided a suitable platform for studying the function of PGC-1α in neuropsychiatric diseases.

Animals ; Female ; Humans ; Interneurons ; metabolism ; Male ; Mice ; Mice, Knockout ; Neurodegenerative Diseases ; genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; genetics ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVE: To investigate the axonal sprouting of somatostatin(SS) positive interneurons in temporal lobe epilepsy. METHODS: 6-8 week-old healthy male SD rats were divided randomly into an epileptic group (treated by lithium and pilocarpine intraperitoneal injection) and a control group (by lithium and normal sodium intraperitoneal injection). Each group was randomly divided into 5 subgroups at 1,7,15,30, amd 60 d after the injection. Immunohistochemistry method was used to detect the number changes of SS or neuronal nuclei (NeuN) positive neurons in different domains of the hippocampus at different time points in each group, and the coexpression of SS positive interneurons combined with NeuN was detected by double immunofluorescence to observe the dynamic changes and axonal sprouting of SS positive interneurons. RESULTS: The number of SS neurons in the experimental group exceeded that in the control group in the CA1 area at 60 d post-status epileptieus SE (P<0.01), and numerous SS positive fibers were seen throughout the layers of the CAl area at 60 d post-SE. NeuN positive neurons in the stratum oriens and stratum radiatum layers in the initiation site of the CA1 area were beyond normal at 60 d post-SE. The number of double labeled SS interneurons gradually rose at 15 d in stratum oriens of CA1, and even exceeded that of the controls in the stratum oriens and stratum radiatum layers of CA1 at 60 d. CONCLUSION The numerous SS positive fibers throughout the layers of the CAl area at 60 d post-SE come from the increased interneurons in the stratum oriens and stratum radiatum layers of CA1 area. The pathological axonal sprouting may play an important role in the generation and compensation of temporal lobe epilepsy.
Animals ; Axons ; metabolism ; pathology ; CA1 Region, Hippocampal ; cytology ; metabolism ; physiopathology ; Efferent Pathways ; pathology ; physiology ; Epilepsy, Temporal Lobe ; chemically induced ; metabolism ; physiopathology ; Interneurons ; cytology ; metabolism ; pathology ; Male ; Pilocarpine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Somatostatin ; metabolism ; Temporal Lobe ; metabolism