Unique Properties of R-Type Calcium Currents in Neocortical and Neostriatal Neurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2225-2236 ◽  
Author(s):  
Robert C. Foehring ◽  
Paul G. Mermelstein ◽  
Wen-Jie Song ◽  
Sasha Ulrich ◽  
D. James Surmeier
Keyword(s):  
Pyramidal Neurons ◽  
Cell Types ◽  
Calcium Currents ◽  
Medium Spiny Neurons ◽  
Cell Type ◽  
Channel Current ◽  
Spiny Neurons ◽  
Deactivation Kinetics ◽  
Whole Cell Recordings ◽  
Neocortical Pyramidal Neurons

Whole cell recordings from acutely dissociated neocortical pyramidal neurons and striatal medium spiny neurons exhibited a calcium-channel current resistant to known blockers of L-, N-, and P/Q-type Ca2+ channels. These R-type currents were characterized as high-voltage–activated (HVA) by their rapid deactivation kinetics, half-activation and half-inactivation voltages, and sensitivity to depolarized holding potentials. In both cell types, the R-type current activated at potentials relatively negative to other HVA currents in the same cell type and inactivated rapidly compared with the other HVA currents. The main difference between cell types was that R-type currents in neocortical pyramidal neurons inactivated at more negative potentials than R-type currents in medium spiny neurons. Ni2+ sensitivity was not diagnostic for R-type currents in either cell type. Single-cell RT-PCR revealed that both cell types expressed the α1E mRNA, consistent with this subunit being associated with the R-type current.

scholarly journals Transcriptional Diversity of Medium Spiny Neurons in the Primate Striatum

2020 ◽  
Author(s):  
Jing He ◽  
Michael Kleyman ◽  
Jianjiao Chen ◽  
Aydin Alikaya ◽  
Kathryn M. Rothenhoefer ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Cell Types ◽  
Specific Information ◽  
Medium Spiny Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Spiny Neurons ◽  
Single Nucleus ◽  
Cell Type Specific

AbstractThe striatum is the neural interface between dopamine reward signals and cortico-basal ganglia circuits responsible for value assignments, decisions, and actions. Medium spiny neurons (MSNs) make up the vast majority of striatal neurons and are traditionally classified as two distinct types: direct- and indirect-pathway MSNs. The direct- and indirect-pathway model has been useful for understanding some aspects of striatal functions, but it accounts for neither the anatomical heterogeneity, nor the functional diversity of the striatum. Here, we use single nucleus RNA-sequencing and Fluorescent In-Situ Hybridization to explore MSN diversity in the Rhesus macaque striatum. We identified MSN subtypes that correspond to the major subdivisions of the striatum. These include dorsal striatum subtypes associated with striosome and matrix compartments, as well as ventral striatum subtypes associated with the shell of the nucleus accumbens. We also describe a cell type that is anatomically restricted to “Neurochemically Unique Domains in the Accumbens and Putamen (NUDAPs)”. Together, these results help to advance nonhuman primate studies into the genomics era. The identified cell types provide a comprehensive blueprint for investigating cell type-specific information processing, and the differentially expressed genes lay a foundation for achieving cell type-specific transgenesis in the primate striatum.

Altered Neuronal Circuitry

2014 ◽  
Author(s):  
Michael S. Levine ◽  
Elizabeth A. Wang ◽  
Jane Y. Chen ◽  
Carlos Cepeda ◽  
Véronique M. André
Keyword(s):  
Mouse Models ◽  
Pyramidal Neurons ◽  
Therapeutic Interventions ◽  
Disease Stage ◽  
Medium Spiny Neurons ◽  
Behavioral Alterations ◽  
Spiny Neurons ◽  
Cortical Pyramidal Neurons ◽  
Late Stages ◽  
Dopamine Modulation

In mouse models of Huntington’s disease (HD), synaptic alterations in the cerebral cortex and striatum are present before overt behavioral symptoms and cell death. Similarly, in HD patients, it is now widely accepted that early deficits can occur in the absence of neural atrophy or overt motor symptoms. In addition, hyperkinetic movements seen in early stages are followed by hypokinesis in the late stages, indicating that different processes may be affected. In mouse models, such behavioral alterations parallel complex biphasic changes in glutamate-mediated excitatory, γ‎-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission and dopamine modulation in medium spiny neurons of the striatum as well as in cortical pyramidal neurons. The progressive electrophysiologic changes in synaptic communication that occur with disease stage in the cortical and basal ganglia circuits of HD mouse models strongly indicate that therapeutic interventions and strategies in human HD must be targeted to different mechanisms in each stage and to specific subclasses of neurons.

scholarly journals Biology and Bias in Cell Type-Specific RNAseq of Nucleus Accumbens Medium Spiny Neurons

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hope Kronman ◽  
Felix Richter ◽  
Benoit Labonté ◽  
Ramesh Chandra ◽  
Shan Zhao ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Medium Spiny Neurons ◽  
Cell Type ◽  
Spiny Neurons ◽  
Cell Type Specific

Calcium Currents in Retrogradely Labeled Pyramidal Cells From Rat Sensorimotor Cortex

2000 ◽  
Vol 83 (4) ◽  
pp. 2349-2354 ◽  
Author(s):  
Ansalan Stewart ◽  
Robert C. Foehring
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Calcium Currents ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Multiple Populations ◽  
Whole Cell Patch Clamp ◽  
The Mean ◽  
P Type

Our previous studies of calcium (Ca2+) currents in cortical pyramidal cells revealed that the percentage contribution of each Ca2+ current type to the whole cell Ca2+ current varies from cell to cell. The extent to which these currents are modulated by neurotransmitters is also variable. This study was directed at testing the hypothesis that a major source of this variability is recording from multiple populations of pyramidal cells. We used the whole cell patch-clamp technique to record from dissociated corticocortical, corticostriatal, and corticotectal projecting pyramidal cells. There were significant differences between the three pyramidal cell types in the mean percentage of L-, P-, and N-type Ca2+ currents. For both N- and P-type currents, the range of percentages expressed was small for corticostriatal and corticotectal cells as compared with cells which project to the corpus callosum or to the general population. The variance was significantly different between cell types for N- and P-type currents. These results suggest that an important source of the variability in the proportions of Ca2+ current types present in neocortical pyramidal neurons is recording from multiple populations of pyramidal cells.

scholarly journals Dysfunction of cAMP-PKA-calcium signaling axis in striatal medium spiny neurons: a role in schizophrenia and Huntington’s disease pathogenesis

2021 ◽  
Author(s):  
Marija Fjodorova ◽  
Zoe Noakes ◽  
Daniel C. De La Fuente ◽  
Adam C. Errington ◽  
Meng Li
Keyword(s):  
Huntington's Disease ◽  
Calcium Signaling ◽  
Huntington’S Disease ◽  
Cortical Neurons ◽  
Medium Spiny Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Direct Role ◽  
Spiny Neurons ◽  
Signaling Axis

SummaryBackgroundStriatal medium spiny neurons (MSNs) are preferentially lost in Huntington’s disease. Genomic studies also implicate a direct role for MSNs in schizophrenia, a psychiatric disorder known to involve cortical neuron dysfunction. It remains unknown whether the two diseases share similar MSN pathogenesis or if neuronal deficits can be attributed to cell type-dependent biological pathways. Transcription factor BCL11B, which is expressed by all MSNs and deep layer cortical neurons, was recently proposed to drive selective neurodegeneration in Huntington’s disease and identified as a candidate risk gene in schizophrenia.MethodsUsing human stem cell-derived neurons lacking BCL11B as a model, we investigated cellular pathology in MSNs and cortical neurons in the context of these disorders. Integrative analyses between differentially expressed transcripts and published GWAS datasets identified cell type-specific disease-related phenotypes.ResultsWe uncover a role for BCL11B in calcium homeostasis in both neuronal types, while deficits in mitochondrial function and protein kinase A (PKA)-dependent calcium transients are detected only in MSNs. Moreover, BCL11B-deficient MSNs display abnormal responses to glutamate and fail to integrate dopaminergic and glutamatergic stimulation, a key feature of striatal neurons in vivo. Gene enrichment analysis reveals overrepresentation of disorder risk genes among BCL11B-regulated pathways, primarily relating to cAMP-PKA-calcium signaling axis and synaptic signaling.ConclusionsOur study indicates that Huntington’s disease and schizophrenia are likely to share neuronal pathogenesis where dysregulation of intracellular calcium levels is found in both striatal and cortical neurons. In contrast, reduction in PKA signaling and abnormal dopamine/glutamate receptor signaling is largely specific to MSNs.

Muscarinic Inhibition of Persistent Na+ Current in Rat Neocortical Pyramidal Neurons

1998 ◽  
Vol 79 (3) ◽  
pp. 1579-1582 ◽  
Author(s):  
Thomas Mittmann ◽  
Christian Alzheimer
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Cholinergic Innervation ◽  
Voltage Range ◽  
Rat Neocortex ◽  
The Rich ◽  
Subthreshold Voltage ◽  
Whole Cell Recordings ◽  
Muscarinic Modulation ◽  
Neocortical Pyramidal Neurons

Mittmann, Thomas and Christian Alzheimer. Muscarinic inhibition of persistent Na+ current in rat neocortical pyramidal neurons. J. Neurophysiol. 79: 1579–1582, 1998. Muscarinic modulation of persistent Na+ current ( I NaP) was studied using whole cell recordings from acutely isolated pyramidal cells of rat neocortex. After suppression of Ca2+ and K+ currents, I NaP was evoked by slow depolarizing voltage ramps or by long depolarizing voltage steps. The cholinergic agonist, carbachol, produced an atropine-sensitive decrease of I NaP at all potentials. When applied at a saturating concentration (20 μM), carbachol reduced peak I NaP by 38% on average. Carbachol did not alter the voltage dependence of I NaP activation nor did it interfere with the slow inactivation of I NaP. Our data indicate that I NaP can be targeted by the rich cholinergic innervation of the neocortex. Because I NaP is activated in the subthreshold voltage range, cholinergic inhibition of this current would be particularly suited to modulate the electrical behavior of neocortical pyramidal cells below and near firing threshold.

scholarly journals Transitions between sleep and feeding states in rat ventral striatum neurons

2012 ◽  
Vol 108 (6) ◽  
pp. 1739-1751 ◽  
Author(s):  
Luis A. Tellez ◽  
Isaac O. Perez ◽  
Sidney A. Simon ◽  
Ranier Gutierrez
Keyword(s):  
Neural Networks ◽  
Ventral Striatum ◽  
Cell Types ◽  
Projection Neurons ◽  
Inhibitory Interneurons ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Fast Spiking ◽  
First Time

Neurons in the nucleus accumbens (NAc) have been shown to participate in several behavioral states, including feeding and sleep. However, it is not known if the same neuron participates in both states and, if so, how similar are the responses. In addition, since the NAc contains several cell types, it is not known if each type participates in the transitions associated with feeding and sleep. Such knowledge is important for understanding the interaction between two different neural networks. For these reasons we recorded ensembles of NAc neurons while individual rats volitionally transitioned between the following states: awake and goal directed, feeding, quiet-awake, and sleeping. We found that during both feeding and sleep states, the same neurons could increase their activity (be activated) or decrease their activity (be inactivated) by feeding and/or during sleep, thus indicating that the vast majority of NAc neurons integrate sleep and feeding signals arising from spatially distinct neural networks. In contrast, a smaller population was modulated by only one of the states. For the majority of neurons in either state, we found that when one population was excited, the other was inhibited, suggesting that they act as a local circuit. Classification of neurons into putative interneurons [fast-spiking interneurons (pFSI) and choline acetyltransferase interneurons (pChAT)] and projection medium spiny neurons (pMSN) showed that all three types are modulated by transitions to and from feeding and sleep states. These results show, for the first time, that in the NAc, those putative inhibitory interneurons respond similarly to pMSN projection neurons and demonstrate interactions between NAc networks involved in sleep and feeding.

scholarly journals Cell-type and endocannabinoid specific synapse connectivity in the adult nucleus accumbens core

2019 ◽  
Author(s):  
Marion A. Deroche ◽  
Olivier Lassalle ◽  
Olivier J. Manzoni
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Basolateral Amygdala ◽  
Ventral Hippocampus ◽  
Cb1 Receptors ◽  
Medium Spiny Neurons ◽  
Cell Type ◽  
Spiny Neurons ◽  
Trpv1 Receptors ◽  
Specific Manner

ABSTRACTThe nucleus accumbens (NAc) is a mesocorticolimbic structure that integrates cognitive, emotional and motor functions. Although its role in psychiatric disorders is widely acknowledged, the understanding of its circuitry is not complete. Here we combined optogenetic and whole-cell recordings to draw a functional portrait of excitatory disambiguated synapses onto D1 and D2 medium spiny neurons (MSNs) in the adult mouse NAc core. Comparing synaptic properties of ventral hippocampus (vHipp), basolateral amygdala (BLA) and prefrontal cortex (PFC) inputs revealed a hierarchy of synaptic inputs and feedforward inhibition that depends on the identity of the postsynaptic target MSN. Thus, the BLA is the dominant excitatory pathway onto D1 MSNs (BLA > PFC = vHipp) while PFC inputs dominate D2 MSNs (PFC > vHipp > BLA). Feedforward inhibition of MSN firing too, was input and cell-type specific: while minimal at vHipp-D1 and vHipp-D2 inputs; it inhibited with similar efficacy BLA-D1 or BLA-D2 inputs, was minimal at PFC-D1 but maximal at PFC-D2 inputs. We also tested the hypothesis that endocannabinoids endow excitatory circuits with pathway- and cell-specific plasticity. Thus, while CB1 receptors (CB1R) uniformly depress excitatory pathways irrespective of MSNs identity, TRPV1 receptors (TRPV1R) bidirectionally control inputs onto the NAc core in a pathway-specific manner. Finally, we show how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses. Together these data shed new light on synapse and circuit specificity in the adult NAc core and illustrate how endocannabinoids contribute to pathway-specific synaptic plasticity.SIGNIFICANCE STATEMENTWe examined the impact of connections from the ventral hippocampus (vHipp,) basolateral amygdala (BLA) and prefrontal cortex (PFC) onto identified medium spiny neurons (MSN) in the adult accumbens core. We found BLA inputs were strongest at D1 MSNs while PFC inputs dominate D2 MSNs. We evaluated the role of the endocannabinoid system in pathway- and cell-specific plasticity and found that CB1 receptors (CB1R) and TRPV1 receptors (TRPV1R) bidirectionally control synaptic transmission and plasticity onto accumbens’ MSNs in a pathway- and cell-specific manner. Finally, we clarify how the interplay of TRPV1R/CB1R shapes plasticity at identified BLA-NAc synapses.

scholarly journals FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kirsty Sawicka ◽  
Caryn R Hale ◽  
Christopher Y Park ◽  
John J Fak ◽  
Jodi E Gresack ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Rna Binding ◽  
Fragile X ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Cell Type ◽  
Ca1 Pyramidal Neurons ◽  
Mrna Targets ◽  
Specific Regulation

Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins. This contrasted with different targets in cerebellar granule neurons, and was consistent with circadian defects in hippocampus-dependent memory in Fmr1 knockout mice. These findings demonstrate differential FMRP-dependent regulation of mRNAs across neuronal cell types that may contribute to phenotypes such as memory defects and sleep disturbance associated with FXS.

scholarly journals Inhibitory ultrapotent chemogenetics activate dopamine D1 receptor-expressing medium spiny neurons

2020 ◽  
Author(s):  
Stephanie C. Gantz ◽  
Maria M. Ortiz ◽  
Andrew J. Belilos ◽  
Khaled Moussawi
Keyword(s):  
Brain Slices ◽  
Reversal Potential ◽  
Cell Types ◽  
Receptor Activation ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Medium Spiny Neurons ◽  
Inhibitory Function ◽  
Spiny Neurons

SUMMARYUltrapotent chemogenetics, including the chloride-permeable inhibitory PSAM4-GlyR receptor, were recently proposed as a powerful strategy to selectively control neuronal activity in awake, behaving animals. We aimed to validate the inhibitory function of PSAM4-GlyR in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) in the ventral striatum. Activation of PSAM4-GlyR with the uPSEM792 ligand enhanced rather than suppressed the activity of D1-MSNs in vivo as indicated by increased c-fos expression in D1-MSNs. Whole-cell recordings in mouse brain slices showed that activation of PSAM4-GlyR did not inhibit firing of action potentials in D1-MSNs. Activation of PSAM4-GlyR depolarized D1-MSNs, attenuated GABAergic inhibition, and shifted the reversal potential of PSAM4-GlyR current to more depolarized potentials, perpetuating the depolarizing effect of receptor activation. The data show that ‘inhibitory’ PSAM4-GlyR chemogenetics may actually activate certain cell types, and highlight the pitfalls of utilizing chloride conductances to inhibit neurons.

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