Spatial Distribution of Parvalbumin-Positive Fibers in the Mouse Brain and Their Alterations in Mouse Models of Temporal Lobe Epilepsy and Parkinson's Disease / 神经科学通报·英文版

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.

Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment / 神经科学通报·英文版

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.

Functional Autapses Form in Striatal Parvalbumin Interneurons but not Medium Spiny Projection Neurons / 神经科学通报·英文版

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 GABAA 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.

Correlation Analysis of Molecularly-Defined Cortical Interneuron Populations with Morpho-Electric Properties in Layer V of Mouse Neocortex / 神经科学通报·英文版

Cortical interneurons can be categorized into distinct populations based on multiple modalities, including molecular signatures and morpho-electrical (M/E) properties. Recently, many transcriptomic signatures based on single-cell RNA-seq have been identified in cortical interneurons. However, whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown. Here, we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA (mRNA) expression of >600 interneurons in layer V of the mouse somatosensory cortex (S1). Subsequently, we identified 11 M/E subtypes, 9 neurochemical cell populations (NCs), and 20 transcriptomic cell populations (TCs) in this cortical lamina. Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically. A similar analysis of layer V interneurons of mouse primary visual cortex (V1) and motor cortex (M1) gave results largely comparable to S1. Comparison between S1, V1, and M1 suggested that, compared to V1, S1 interneurons were morpho-electrically more similar to M1. Our study reveals the presence of substantial M/E variations in cortical interneuron populations defined by molecular expression.

Proteínas y enzimas como posibles mensajeros en la comunicación química interneuronal. Parte I / Proteins and enzymes as chemical messangers regulating neuronal transmission. First part

En los últimos 30 años un extenso cúmulo de información ha sido reportada sobre la identificación y caracterización fisiológica y molecular de las proteínas y las enzimas; cuya liberación espontánea e inducida a partir del tejido neuronal y de los tejidos extraneuronales, como las células cromafines de la glándula suprarrenal, han permitido no sólo la subsecuente clonación y aislamiento molecular de estas moléculas protéicas, sino que, además, mediante la aplicación de métodos de hibridación in situ, de la generación de anticuerpos selectivos, conjuntamente con el apoyo de técnicas inmunohistoquímicas, se ha podido detectar el origen, localización y expresión celular de enzimas como la acetilcolinesterasa específica (AChE), y la dopamina-betahidroxilasa (DBH), en diversas regiones del cerebro de distintas especies mamíferas, de donde se ha encontrado su capacidad para ejercer funciones neurotróficas. Asimismo, se han abordado similares planteamientos experimentales para identificar y localizar la expresión celular y subcelular de proteínas como las de la familia de los polipéptidos, representados por las cromograninas y las secretoneurinas, que son polipéptidos, cuya síntesis celular modificaciones postraduccionales, almacenamiento y segregación vesicular, como su exocitosis celular en el tejido neuronal y en los tejidos neuroendocrinos, han sido estudiadas in vivo e in vitro a partir de diferentes preparaciones biológicas, cuyos resultados han sido motivo de múltiples publicaciones. Más aún, estas proteínas parecen ser precursoras de varios péptidos bioactivos, en los que se han observado diversas funciones de tipo autocrino, paracrino, o endocrino, en el tejido neuronal y en los tejidos extraneuronales. Asimismo, una extensa familia de factores tróficos, conocidos como neurotrofinas, incluyendo el Factor de Crecimiento Neuronal (NGF), recientemente se aislaron, identificaron, y caracterizaron molecular y funcionalmente, in vivo e in vitro, con lo que se demostró su capacidad para regular y mantener la supervivencia de diferentes poblaciones de células neuronales en el sistema nervioso central y periférico de múltiples especies de vertebrados e invertebrados, lo que parece mediarse por la activación de diversos subgrupos de receptores membranales, recientemente identificados y localizados en discretas poblaciones neuronales

Specificity of synapse formation in the cockroach

Las conecciones sinápticas entre las neuronas sensoriales de los pelos filiformes (FHSNs) y las interneuronas gigantes (GIs) en el ganglio terminal abdominal del primer estadió ninfal de la cucaracha Periplaneta americana han sido utilizado como sistema modelo para investigar los mecanismos de especificidad en la formación de sinapsis. Técnicas de electrofisiología y microscopía electrónica fueron usadas con el fin de establecer los circuitos normales de conección entre FHSNs y GIs. Se encontró que durante el período de "sinaptogénesis" no hubo equivocación al formarse las sinápsis entre los axones sensoriales y las dendritas de las interneuronas correspondientes. Estudios con un mutante que posee un axon sensorial adicional han arrojado nueva luz sobre la función de la información posicional para determinar la forma y las conecciones de la neurona sensorial con las GIs. Ha sido obtenida evidencia electrofisiológica de interacciones competitivas entre el axon sensorial adicional y el original