Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “medium spiny neurons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

11 recordsLinked to original sources
PubMed2026

Loss of interruption in the HTT CAG repeat is associated with somatic expansion and loss of medium spiny neurons in Huntington's disease.

Synonymous loss-of-interruption variants in the expanded CAG repeat sequence of Huntingtin (HTT) accelerate the clinical onset and progression of Huntington's disease (HD). Medium spiny neurons (MSNs) are gradually lost in HD and undergo selective somatic CAG expansion, but it is unclear how somatic expansion relates to MSN pathology. Here, we show that MSNs with large (111-150 CAG) and very large (>150 CAG) somatic expansions are rare in early manifest HD but accumulate in proportion with duration of disease. In patients with the deleterious CAG-CCG loss-of-interruption (CAG-CCG LOI) modifier, the proportion of MSNs with large and very large expansions is increased ∼5-fold despite reduced small somatic expansions in blood, and caudate MSN counts are reduced. Our findings suggest that increased somatic CAG expansion contributes to accelerated striatal MSN pathology and onset of HD but that MSNs with very large genomic CAG expansions can persist among surviving neurons of the HD brain.

Huntington’s disease↗
PubMed1978

Response properties and electrical constants of caudate nucleus neurons in the cat.

1. Response properties and passive electrical constants were assessed for caudate nucleus neurons in pentobarbital-anesthetized cats. The neurons studied were those which could be monosynaptically excited by substantia nigra and thalamic (centromedian-parafascicular) stimulation. 2. Input resistance and membrane time constant were estimated from the plateau value and time course, respectively, of the neuronal membrane response to intracellularly applied current pulses. The average values obtained were 16.5 Momega and 11.3 ms. Specific resistance and capacitance values were calculated. 3. Single or repetitive spikes were readily evoked by nigral or thalamic stimuli or by the application of direct depolarizing currents. Spike thresholds were higher for direct than for synaptic activation (7.2 vs. 5.6 mV). 4. Direct depolarizing stimuli with durations up to 600 ms elicited repetitive discharge with little adaptation of firing rate. The maximum discharge rates induced by direct stimuli were near 200 spikes per second. 5. The intracellular application of tetraethylammonium chloride (TEA) produced spike-prolongation effects in caudate neurons that were similar to the effects reported for other nerve membrane. 6. The probable identity of the recorded neurons as medium spiny neurons was discussed and, in addition, it was proposed that the characteristic silence of these cells is not likely due to intrinsic membrane specialization.

Action Potentials↗
PubMed2026

Refinement of Nucleus Accumbens Neuronal Dynamics during Cocaine Self-Administration Training.

Drug addiction is an acquired motivational-behavioral state that begins with drug taking, which is composed of a series of phases, including initial acquisition, stabilization, habituation, and maintenance. In rodent models of cocaine self-administration, the forebrain region nucleus accumbens (NAc) has been critically implicated in the acquisition-maintenance process of drug-taking and drug-seeking behaviors. However, it remains unknown how NAc neurons shift their activity patterns in response to these phasic transitions during cocaine taking. To examine this, we used GCaMP6m-based in vivo Ca2+ imaging in male mice to monitor activities of principal medium spiny neurons (MSNs) in the NAc across 11 d of cocaine self-administration. Behaviorally, mice exhibited progressive stabilization of operant responding and locomotion across 11 d of cocaine self-administration. During the early training days, we detected a portion of NAc neurons-a potential neuronal ensemble-that exhibited increased activities temporally contingent to the lever-press for cocaine. The number of NAc neurons exhibiting contingent activity increased progressively over the first three training days and then decreased gradually during the later training days, exhibiting expansion-refinement dynamics that may correspond to the acquisition and subsequent stabilization/maintenance of cocaine self-administration. Using a neuron-tracking technique, we found that the lever-press-contingent NAc ensemble exhibited substantial compositional dynamics, with neurons dropping into and out across training days. These activity features of lever-press-contingent neurons may represent key circuit dynamics of the NAc that transition the acquisition toward the maintenance of cocaine-taking behavior.

Animals↗
PubMed2026

Visualizing synaptic disruptions in the release and regulation of dopamine hotspots in Huntington's Disease.

Dopamine neuromodulation is a critical process that facilitates learning, motivation, and motor control. Disruption of these processes has been implicated in several neurodegenerative disorders including Huntington's Disease (HD). While dopaminergic signaling is a therapeutic target for treating physical and psychiatric HD symptoms, the mechanism by which dopaminergic dysfunction occurs during HD is unknown. New tools for the visualization of dopamine dynamics at the spatiotemporal resolution of neuromodulator release (ms) and dopaminergic boutons (µm) provide a richer understanding of how dopamine signaling is disrupted in HD. Here we employ near-infrared fluorescent catecholamine nanosensors (nIRCats) to image dopamine release within the striatum of R6/2 Huntington's Disease model mice of either sex. We find that dorsal striatal dopamine release decreases with progressive degeneration and that these deficits are primarily driven by a decrease in the number of nIRCat imaged dopamine release sites, termed dopamine hotspots, combined with decreased release fidelity. Using nIRCat's high spatial resolution, we track individual dopamine hotspots over repeated stimulations and pharmacological applications to measure dopamine release fidelity from individual sites. Compellingly, we found that D2-receptor (D2R) antagonist sulpiride drives increased fidelity of dopamine hotspot activity in wild type striatum but not in late-disease HD striatum, suggesting that D2R regulation of dopamine release is compromised in late HD. These findings, enabled by nIRCats, provide more detailed insights into how dopamine release is disrupted and dysregulated during Huntington's Disease.Significance statement Huntington's Disease (HD) is a neurodegenerative disorder with no cure. Dopamine signaling is known to deteriorate in HD but has not been studied at the level of individual release sites. Here, we image dopamine release from individual dopamine release sites in R6/2 HD mouse brain slices containing the striatum with novel dopamine nanosensors. We find that dopamine release site number and release fidelity are decreased in late HD. Furthermore, we demonstrate that D2-receptor signaling may be altered in late disease R6/2 HD mice, and that these disruptions are likely to drive decreased dopamine release fidelity over multiple stimulations. These findings suggest dopaminergic neurons projecting to the striatum as a potential therapeutic target for HD treatment to complement more commonly targeted medium spiny neurons.

Journal Article↗
PubMed2026

Targeting DNA mismatch repair in Huntington's disease.

Somatic expansion of the HTT CAG repeat is a key feature of Huntington's disease (HD) pathogenesis. Mismatch repair (MMR) enzymes drive this process through erroneous DNA repair, with variants in MMR genes modifying the onset and progression of disease features. Cell-type-specific CAG repeat sizing recently confirmed that elevated somatic expansion underlies the selective vulnerability of HD medium spiny neurons, with expansion beyond certain CAG thresholds associated with distinct stages of cellular pathogenesis. In this review, we synthesise insights from post-mortem brain tissue, cell systems, and mouse models, detailing key CAG repeat-length-dependent changes. In addition, we critically evaluate the MMR proteins MSH3, MLH3, and PMS1 as therapeutic targets for slowing somatic expansion and outline key safety considerations for emerging MMR-modulating approaches.

Huntington Disease↗
PubMed2026

E2F3a transcription factor mediates behavioral, cellular, and DNA-protein regulation of cocaine reward in the nucleus accumbens.

Drug addiction is characterized by orchestrated transcriptional changes in brain reward regions, including the nucleus accumbens (NAc). The transcription factor E2F3a has emerged as a novel regulator of cocaine's rewarding effects, yet its sex- and cell-specific mechanisms, as well as its genome-wide targets, remain undetermined. Here, we investigated the motivational and reinforcing roles of E2F3a in cocaine reward using conditioned place preference (CPP) and self-administration, combined with behavioral economics and viral-mediated gene manipulation. Selective overexpression of E2F3a in D1-type medium spiny neurons (MSNs), but not D2-MSNs, increased cocaine CPP in both male and female mice, whereas knockdown produced the opposite effects. Behavioral economics analyses further revealed that E2F3a regulates specific aspects of cocaine reinforcement. Genome-wide mapping revealed increased E2F3a binding to DNA at genes associated with cocaine exposure. Together, these results establish E2F3a as a central substrate of cocaine reward via the recruitment of D1-MSNs and coordinated expression of both proven and new molecular drivers.

Journal Article↗
PubMed1979

Projection of neostriatal spiny neurons to the substantia nigra. Application of a combined Golgi-staining and horseradish peroxidase transport procedure at both light and electron microscopic levels.

One type of striatonigral neuron in the rat has been characterized. Golgi impregnation of striatal neurons that had been retrogradely labeled by horseradish peroxidase has shown that the medium-sized, densely spiny neurons project to the substantia nigra. Some of the synapses on three of these identified striatonigral neurons have been studied in the electron microscope following replacement of the Golgi deposit by means of the 'gold-toning' method. Synapsing axonal boutons were found on the following sites: soma and axon initial segment (symmetrical, with flattened or pleomorphic vesicles); primary and secondary dendritic shafts (symmetrical with pleomorphic vesicles); dendritic spines (asymmetrical, with spheroidal vesicles). These findings show that new information concerning neuronal connectivity can be obtained by combining three classical procedures in the same material: first, the Golgi method, that characterizes the type of neuron on the basis of its dendritic morphology; second, a retrograde tracing method, that identifies the projection area of the neuron; and, third, ultrastructural analysis of the nature of afferent terminals on the neuron.

Animals↗
PubMed1977

The neurons and their postnatal development in the ventral lateral geniculate nucleus of the rat.

The morphology and distribution of neurons in the ventral lateral geniculate nucleus (vLGN) of adult rats, and the postnatal growth and differentiation of these neurons were studied in Golgi-Cox preparations. In the adult, two main cell classes were recognized: class A cells and class B cells. The former are assumed to be projection neurons. The latter closely resemble the class B cells of the dorsal lateral geniculate nucleus and are interpreted as presynaptic dendrite-bearing interneurons. Class A cells predominated and three subtypes were tentatively identified: small--medium size multipolar neurons, with short, branched spiny dendrites (most numerous in dorsolateral vLGN); medium--large fusiform cells with one or two stem dendrites at each pole (most numerous in medial vLGN); large multipolar neurons with long, sparsely branched dendrites (most numerous in ventral vLGN). Class A and B cells were distinguishable at birth and showed parallel cell body size increases up to postnatal day 24. The dendrites of both classes of cell also reached the adult stage of differentiation at about day 24 but the differentiation of class B cell dendrites lags slightly behind that of class A cell dendrites.

Animals↗
PubMed1976

A Golgi study of neuronal types in the neostriatum of monkeys.

Examination of the nestriatum of monkeys prepared by the Golgi-Kopsch perfusion method revealed the presence of at least 6 neuronal types. The spiny type I is medium size with a high density of dendritic spines. The axon extends well beyond the dendritic field and gives off many collaterals. The spiny type II is either medium or large size, has long thick dendrites with a relatively low density of spines, and an axon similar to that of the previous type but with fever collaterals. The aspiny type I is medium size with varicose dendrites and a thin axon arborizing in the immediate vicinity of the soma. The aspiny type II is large, with many thick and thin varicose dendrites. The aspiny type III is medium size with smooth dendrites and an axon ramifying profusely within the dendritic field. The neurogliform cell is small with many branching processes. Findings indicate that the neostriatum has 2 distinct types of spiny neurons with long axons (spiny I and II), some of which may contribute to the efferent system. There are also 2 (aspiny I and III) or perhaps as many as 4 categories (aspiny I, II, III and neurogliform) of typical Golgi type II cells. Large neurons belong to 2 separate populations, one with dendritic spines and a long axon (large version of spiny II), and one with varicosities and presumably a short axon (aspiny II). A realistic interpretation of neurophysiologic data on the neostriatum must take into account all cell types instead of the current view of considering it as a pool of interneurons with few output cells.

Animals↗
PubMed1978

Meganeurites and other aberrant processes of neurons in feline GM1-gangliosidosis: a Golgi study.

Golgi studies were carried out on neurons in several forebrain structures of young adult mutant cats with inherited beta-galactosidase deficiency and neurobehavioral deterioration due to GM1-ganglioside storage disease. Meganeurites similar to those observed in several human gangliosidoses were present on small and medium pyramidal neurons, granule cells of the fascia dentata and spiny neurons of the caudate nucleus. Large and giant pyramidal cells of the motor cortex exhibited prominent somatic spines but lacked meganeurites. Cortical non-pyramidal neurons and aspiny caudate cells were relatively normal in appearance although they showed variable increases in cell body diameter. The range of morphological alterations in different types of cortical neurons in feline GM1-gangliosidosis was identical to that found in human ganglioside storage diseases. Neurite outgrowth from meganeurites was particularly prominent in the feline mutant. The extensive proliferation of neurites confined to meganeurites indicates that the latter have growth properties typical of embryonic neuronal elements. The demonstration of neurite outgrowth from meganeurites of mature cortical neurons in feline GM1-gangliosidosis suggests a possible role for gangliosides in neurite formation during neuronal differentiation and synaptogenesis.

Animals↗
PubMed1979

A Golgi study of the ventral tegmental area of Tsai and interfascicular nucleus in the rat.

The ventral tegmental area of Tsai (VTA) and interfascicular nucleus of the adult rat brain has been studied with two variants of the Golgi method in three planes of section. Neurons were studied in relation to the cytoarchitectural groupings of the VTA. Dendritic organisation and dendritic fields were mapped out for each cytoarchitectural subgroup and cell types within each subgroup were classified on the basis of cell size and dendritic morphology. In each subnucleus of VTA, neurons had distinct characteristics. In nucleus paranigralis neurons were small to medium in size and their dendritic fields organised in an approximately horizontal plane orientated in an anteromedial direction and slanting dorsally over the interpeduncular nucleus and fossa. Neurons of the parabrachial group were small to medium sized with no preferential orientation. In nucleus linearis raphe caudalis small neurons were strongly orientated in the plane of the nucleus in a dorso-ventral direction slanting forwards. Neurons in the interfascicular group were small to very small and their maximum dendritic extents were seen in the horizontal plane. In frontal section they formed a compact ball of cells in the midline and were separated on either side from the larger neurons in the medial edge of nucleus paranigralis. In general VTA neurons tended to fall into one of two morphological categories. Type 1 were small to medium, and had two to four primary dendrites which divided into varicose secondary dendrites. Type 2 were medium sized, with two to five primary dendrites. Both primary and secondary dendrites and the cell soma of Type 2 neurons were moderately spiny. Secondary dendrites were not varicose. Forms also occurred which were intermediate between Types 1 and 2. In the nucleus paranigralis, Type 1 was more common medially, while Type 2 was more common laterally, particularly in the ventrolateral paranigral region. Only neurons of Type 1 were seen in nucleus linearis raphe and interfascicular nuclei. Local axon circuits were observed to arise from the primary dendrites of Type 1 neurons and to ramify close to neighbouring neurons. Axon swellings from such circuits were observed to make apparent contact with primary dendrites of nearby neurons and clusters of axon swellings were observed near cell somas of neighbouring impregnated neurons of similar type. The results are discussed and particular attention is paid to the similarities and differences between VTA and the substantia nigra pars compacts (SNC). The major difference appears to be that, whereas in SNC dendrites are organised in vertical as well as horizontal planes, in the VTA no long ventrally directed dendrites were observed. Combining these results with known cytoarchitecture and connections of VTA and SNC, it appears that fundamental differences occur between VTA and some neurons of the SNC, both in the nature of their morphology and intrinsic organisation, and in the organisation of their efferent and afferent connections.

Animals↗