2,574 results match your criteria cholinergic interneurons

Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord.

Nat Commun 2021 04 30;12(1):2471. Epub 2021 Apr 30.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

In vertebrates, motor control relies on cholinergic neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these neurons and their different functional roles in the adult remain to be defined. Here, we develop a targeted single nuclear RNA sequencing approach and use it to identify an array of cholinergic interneurons, visceral and skeletal motor neurons. Our data expose markers for distinguishing these classes of cholinergic neurons and their rich diversity. Read More

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Recurrent Implication of Striatal Cholinergic Interneurons in a Range of Neurodevelopmental, Neurodegenerative, and Neuropsychiatric Disorders.

Cells 2021 Apr 15;10(4). Epub 2021 Apr 15.

Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.

Cholinergic interneurons are "gatekeepers" for striatal circuitry and play pivotal roles in attention, goal-directed actions, habit formation, and behavioral flexibility. Accordingly, perturbations to striatal cholinergic interneurons have been associated with many neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The role of acetylcholine in many of these disorders is well known, but the use of drugs targeting cholinergic systems fell out of favor due to adverse side effects and the introduction of other broadly acting compounds. Read More

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Roles of the Functional Interaction between Brain Cholinergic and Dopaminergic Systems in the Pathogenesis and Treatment of Schizophrenia and Parkinson's Disease.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Pharmacology Laboratory, College of Pharmacy, Chonnam National University, Gwang-Ju 61186, Korea.

Most physiologic processes in the brain and related diseases involve more than one neurotransmitter system. Thus, elucidation of the interaction between different neurotransmitter systems could allow for better therapeutic approaches to the treatments of related diseases. Dopaminergic (DAergic) and cholinergic neurotransmitter system regulate various brain functions that include cognition, movement, emotion, etc. Read More

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Gsx1 promotes locomotor functional recovery after spinal cord injury.

Mol Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854, USA. Electronic address:

Promoting residential cells, particularly endogenous neural stem and progenitor cells (NSPCs), for tissue regeneration represents a potential strategy for the treatment of spinal cord injury (SCI). However, adult NSPCs differentiate mainly into glial cells and contribute to glial scar formation at the site of injury. Gsx1 is known to regulate the generation of excitatory and inhibitory interneurons during embryonic development of the spinal cord. Read More

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Cell-intrinsic effects of TorsinA(ΔE) disrupt dopamine release in a mouse model of TOR1A dystonia.

Neurobiol Dis 2021 Apr 21;155:105369. Epub 2021 Apr 21.

Department of Pharmacology and Chemical Biology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA. Electronic address:

TOR1A-associated dystonia, otherwise known as DYT1 dystonia, is an inherited dystonia caused by a three base-pair deletion in the TOR1A gene (TOR1AΔE). Although the mechanisms underlying the dystonic movements are largely unknown, abnormalities in striatal dopamine and acetylcholine neurotransmission are consistently implicated whereby dopamine release is reduced while cholinergic tone is increased. Because striatal cholinergic neurotransmission mediates dopamine release, it is not known if the dopamine release deficit is mediated indirectly by abnormal acetylcholine neurotransmission or if Tor1a(ΔE) acts directly within dopaminergic neurons to attenuate release. Read More

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A spotlight on the elusive striatal cholinergic interneuron.

Science 2021 04;372(6540):345-346

Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.

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Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice.

Science 2021 04;372(6540)

Department of Neurology, Duke University Medical Center, Durham, NC 27715, USA.

The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Read More

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Induction of cellular senescence as a late effect and BDNF-TrkB signaling-mediated ameliorating effect on disruption of hippocampal neurogenesis after developmental exposure to lead acetate in rats.

Toxicology 2021 Apr 20;456:152782. Epub 2021 Apr 20.

Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan; Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan; Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. Electronic address:

Lead (Pb) exposure causes cognitive deficits in children. The present study investigated the effect of developmental exposure to Pb acetate (PbAc) on postnatal hippocampal neurogenesis. Pregnant rats were administered drinking water containing 0, 2000, or 4000 ppm PbAc from gestational day 6 until day 21 post-delivery (weaning), and offspring were maintained without PbAc exposure until adulthood on postnatal day (PND) 77. Read More

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Er81 transcription factor Fine-tunes Striatal Cholinergic Interneuron Activity and Drives Habit Formation.

J Neurosci 2021 Apr 10. Epub 2021 Apr 10.

Eccles Institute of Neuroscience, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia

The molecular mechanisms tuning cholinergic interneuron (CIN) activity, although crucial for striatal function and behaviour, remain largely unexplored. Previous studies report that the Etv1/Er81 transcription factor is vital for regulating neuronal maturation and activity. Whilst Er81 is known to be expressed in the striatum during development, its specific role in defining CIN properties and the resulting consequences on striatal function is unknown. Read More

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Parafascicular Thalamic and Orbitofrontal Cortical Inputs to Striatum Represent States for Goal-Directed Action Selection.

Front Behav Neurosci 2021 19;15:655029. Epub 2021 Mar 19.

Centre for Neuroscience and Regenerative Medicine, University of Technology Sydney, Sydney, NSW, Australia.

Several lines of evidence accrued over the last 5-10 years have converged to suggest that the parafascicular nucleus of the thalamus and the lateral orbitofrontal cortex each represent or contribute to internal state/context representations that guide action selection in partially observable task situations. In rodents, inactivations of each structure have been found to selectively impair performance in paradigms testing goal-directed action selection, but only when that action selection relies on state representations. Electrophysiological evidence has suggested that each structure achieves this function inputs onto cholinergic interneurons (CINs) in the dorsomedial striatum. Read More

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Ablation of p75 signaling strengthens gamma-theta rhythm interaction and counteracts Aβ-induced degradation of neuronal dynamics in mouse hippocampus in vitro.

Transl Psychiatry 2021 Apr 9;11(1):212. Epub 2021 Apr 9.

Neuronal Oscillations Laboratory, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, 17164, Solna, Sweden.

Gamma and theta brain rhythms play important roles in cognition and their interaction can affect gamma oscillation features. Hippocampal theta oscillations depend on cholinergic and GABAergic input from the medial septum-diagonal band of Broca. These projecting neurons undergo degeneration during aging and maintain high levels of neurotrophin receptor p75 (p75). Read More

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Revisiting dopamine-acetylcholine imbalance in Parkinson's disease: Glutamate co-transmission as an exciting partner in crime.

Neuron 2021 04;109(7):1070-1071

Department of Physiology, Anatomy and Genetics, and Oxford Parkinson's Disease Centre, University of Oxford, Oxford OX1 3PT, UK. Electronic address:

Striatal dopamine and acetylcholine are thought to be imbalanced in Parkinson's disease. In this issue of Neuron, Cai et al. report that restoration of nigral glutamate co-transmission, acting on dorsolateral striatal cholinergic interneuron mGluR1s, can rescue motor dysfunction in a mouse model of Parkinson's. Read More

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Brainstem Neuronal Circuitries Controlling Gastric Tonic and Phasic Contractions: A Review.

Cell Mol Neurobiol 2021 Apr 3. Epub 2021 Apr 3.

Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, 20007, USA.

This review is on how current knowledge of brainstem control of gastric mechanical function unfolded over nearly four decades from the perspective of our research group. It describes data from a multitude of different types of studies involving retrograde neuronal tracing, microinjection of drugs, whole-cell recordings from rodent brain slices, receptive relaxation reflex, accommodation reflex, c-Fos experiments, immunohistochemical methods, electron microscopy, transgenic mice, optogenetics, and GABAergic signaling. Data obtained indicate the following: (1) nucleus tractus solitarius (NTS)-dorsal motor nucleus of the vagus (DMV) noradrenergic connection is required for reflex control of the fundus; (2) second-order nitrergic neurons in the NTS are also required for reflex control of the fundus; (3) a NTS GABAergic connection is required for reflex control of the antrum; (4) a single DMV efferent pathway is involved in brainstem control of gastric mechanical function under most experimental conditions excluding the accommodation reflex. Read More

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A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice.

Int J Mol Sci 2021 Mar 7;22(5). Epub 2021 Mar 7.

Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy.

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/- knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. Read More

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Dorsal and ventral striatal neuronal subpopulations differentially disrupt male mouse copulatory behavior.

Eur Neuropsychopharmacol 2021 Mar 26;49:23-37. Epub 2021 Mar 26.

Laboratory of Neurophysiology, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), Brussels B-1070, Belgium. Electronic address:

The specific role of the striatum, especially its dorsolateral (DLS) and dorsomedial (DMS) parts, in male copulatory behavior is still debated. In order to clarify their contribution to male sexual behavior, we specifically ablated the major striatal neuronal subpopulations, direct and indirect medium spiny neurons (dMSNs and iMSNs) in DMS or DLS, and dMSNs, iMSNs and cholinergic interneurons in nucleus accumbens (NAc), The main results of this study can be summarized as follows: In DMS, dMSN ablation causes a reduction in the percent of mice that mount a receptive female, and a complex alteration in the parameters of the copulatory performance, that is largely opposite to the alterations induced by iMSN ablation. In DLS, dMSN ablation causes a widespread alteration in the copulatory behavior parameters, that tends to disappear at repetition of the test; iMSN ablation induces minor copulatory behavior alterations that are complementary to those observed after dMSN ablation. Read More

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Rhythmogenic networks are potently modulated by activation of muscarinic acetylcholine receptors in the rodent spinal cord.

J Neurochem 2021 Mar 18. Epub 2021 Mar 18.

Department of Medical Neurobiology, Institute for Medical Research - Israel-Canada, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Electrical stimulation of the spinal cord is a potent means for activating mammalian stepping in the absence of the descending control from the brain. Previously, we have shown that stimulation of pain delivering (Aδ) sacrocaudal afferents (SCA) has a powerful capacity to activate the sacral and lumbar rhythmogenic networks in the neonatal rodent spinal cord. Relatively little is known about the neural pathways involved in activation of the locomotor networks by Aδ afferents, on their mechanism of action and on the possibility to modulate their activity. Read More

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Lateral ventral tegmental area GABAergic and glutamatergic modulation of conditioned learning.

Cell Rep 2021 Mar;34(11):108867

Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland. Electronic address:

The firing activity of dorso-medial-striatal-cholinergic interneurons (dmCINs) is a neural correlate of classical conditioning. Tonically active, they pause in response to salient stimuli, mediating acquisition of predictive cues/outcome associations. Cortical and thalamic inputs are typical of the rather limited knowledge about underlying circuitry contributing to this function. Read More

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LONP1 Regulates Mitochondrial Accumulations of HMGB1 and Caspase-3 in CA1 and PV Neurons Following Status Epilepticus.

Int J Mol Sci 2021 Feb 25;22(5). Epub 2021 Feb 25.

Department of Anatomy and Neurobiology, Institute of Epilepsy Research, College of Medicine, Hallym Unversity, Chuncheon 24252, Korea.

Lon protease 1 (LONP1) is a highly conserved serine peptidase that plays an important role in the protein quality control system in mammalian mitochondria. LONP1 catalyzes the degradation of oxidized, dysfunctional, and misfolded matrix proteins inside mitochondria and regulates mitochondrial gene expression and genome integrity. Therefore, LONP1 is up-regulated and suppresses cell death in response to oxidative stress, heat shock, and nutrient starvation. Read More

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February 2021

Coordinated Postnatal Maturation of Striatal Cholinergic Interneurons and Dopamine Release Dynamics in Mice.

J Neurosci 2021 Apr 4;41(16):3597-3609. Epub 2021 Mar 4.

Departments of Psychiatry, Neurology, Pharmacology, Columbia University Irving Medical Center, New York, New York 10032

Dynamic changes in motor abilities and motivated behaviors occur during the juvenile and adolescent periods. The striatum is a subcortical nucleus critical to action selection, motor learning, and reward processing. Its tonically active cholinergic interneuron (ChI) is an integral regulator of the synaptic activity of other striatal neurons, as well as afferent axonal projections of midbrain dopamine (DA) neurons; however, little is known about its development. Read More

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How predictive learning influences choice: Evidence for a GPCR-based memory process necessary for Pavlovian-instrumental transfer.

J Neurochem 2021 Mar 4. Epub 2021 Mar 4.

Decision Neuroscience Laboratory, School of Psychology, UNSW SYDNEY, Randwick, NSW, Australia.

Predictive learning endows stimuli with the capacity to signal both the sensory-specific and general motivational properties of their associated rewards or outcomes. These two signals can be distinguished behaviorally by their influence on the selection and performance of instrumental actions, respectively. This review focuses on how sensory-specific predictive learning guides choice between actions that earn otherwise equally desirable outcomes. Read More

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Rapid multi-directed cholinergic transmission in the central nervous system.

Nat Commun 2021 03 2;12(1):1374. Epub 2021 Mar 2.

Department of Biology, University of Victoria, Victoria, BC, Canada.

In many parts of the central nervous system, including the retina, it is unclear whether cholinergic transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale 'non-synaptic' mechanisms. Here, we characterized the ultrastructural features of cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a 'tripartite' structure facilitates a 'multi-directed' form of transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Read More

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Make a Left Turn: Cortico-Striatal Circuitry Mediating the Attentional Control of Complex Movements.

Mov Disord 2021 03 22;36(3):535-546. Epub 2021 Feb 22.

Department of Psychology & Neuroscience Program, University of Michigan, Ann Arbor, Michigan, USA.

Background: In movement disorders such as Parkinson's disease (PD), cholinergic signaling is disrupted by the loss of basal forebrain cholinergic neurons, as well as aberrant activity in striatal cholinergic interneurons (ChIs). Several lines of evidence suggest that gait imbalance, a key disabling symptom of PD, may be driven by alterations in high-level frontal cortical and cortico-striatal processing more typically associated with cognitive dysfunction.

Methods: Here we describe the corticostriatal circuitry that mediates the cognitive-motor interactions underlying such complex movement control. Read More

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Loss of nigral excitation of cholinergic interneurons contributes to parkinsonian motor impairments.

Neuron 2021 04 17;109(7):1137-1149.e5. Epub 2021 Feb 17.

Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

Progressive loss of dopamine inputs in Parkinson's disease leads to imbalances in coordinated signaling of dopamine and acetylcholine (ACh) in the striatum, which is thought to contribute to parkinsonian motor symptoms. As reciprocal interactions between dopamine inputs and cholinergic interneurons (ChIs) control striatal dopamine and ACh transmission, we examined how partial dopamine depletion in an early-stage mouse model for Parkinson's disease alters nigral regulation of cholinergic activity. We found region-specific alterations in how remaining dopamine inputs regulate cholinergic excitability that differ between the dorsomedial (DMS) and dorsolateral (DLS) striatum. Read More

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Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models.

PLoS Comput Biol 2021 Feb 18;17(2):e1008737. Epub 2021 Feb 18.

Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.

Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory systems have been proposed as key to facilitate these transitions. Although whole-brain computational models have reproduced this neuromodulatory effect, the role of local inhibitory circuits and their cholinergic modulation has not been studied. Read More

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February 2021

Enhanced GABAergic Inhibition of Cholinergic Interneurons in the zQ175 Mouse Model of Huntington's Disease.

Front Syst Neurosci 2020 20;14:626412. Epub 2021 Jan 20.

Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that initially manifests itself in the striatum. How intrastriatal circuitry is altered by the disease is poorly understood. To help fill this gap, the circuitry linking spiny projection neurons (SPNs) to cholinergic interneurons (ChIs) was examined using electrophysiological and optogenetic approaches in brain slices from wildtype mice and zQ175 models of HD. Read More

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January 2021

Levodopa Causes Striatal Cholinergic Interneuron Burst-Pause Activity in Parkinsonian Mice.

Mov Disord 2021 Feb 6. Epub 2021 Feb 6.

Universidad de Buenos Aires, CONICET, Instituto de Fisiología y Biofísica (IFIBIO) Bernardo Houssay, Grupo de Neurociencia de Sistemas, 2155 Paraguay Street, Buenos Aires, 1121, Argentina.

Background: Enhanced striatal cholinergic interneuron activity contributes to the striatal hypercholinergic state in Parkinson's disease (PD) and to levodopa-induced dyskinesia. In severe PD, dyskinesia and motor fluctuations become seriously debilitating, and the therapeutic strategies become scarce. Given that the systemic administration of anticholinergics can exacerbate extrastriatal-related symptoms, targeting cholinergic interneurons is a promising therapeutic alternative. Read More

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February 2021

Striatal cholinergic transmission. Focus on nicotinic receptors' influence in striatal circuits.

Maxime Assous

Eur J Neurosci 2021 Apr 26;53(8):2421-2442. Epub 2021 Apr 26.

Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey, Newark, NJ, USA.

The critical role of acetylcholine (ACh) in the basal ganglia is evident from the effect of cholinergic agents in patients suffering from several related neurological disorders, such as Parkinson's disease, Tourette syndrome, or dystonia. The striatum possesses the highest density of ACh markers in the basal ganglia underlying the importance of ACh in this structure. Striatal cholinergic interneurons (CINs) are responsible for the bulk of striatal ACh, although extrinsic cholinergic afferents from brainstem structures may also play a role. Read More

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Investigating the role of striatal dopamine receptor 2 in motor coordination and balance: Insights into the pathogenesis of DYT1 dystonia.

Behav Brain Res 2021 Apr 18;403:113137. Epub 2021 Jan 18.

Norman Fixel Institute for Neurological Diseases, Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, United States; Genetics Institute, University of Florida, Gainesville, FL, United States. Electronic address:

DYT1 or DYT-TOR1A dystonia is early-onset, generalized dystonia. Most DYT1 dystonia patients have a heterozygous trinucleotide GAG deletion in DYT1 or TOR1A gene, with a loss of a glutamic acid residue of the protein torsinA. DYT1 dystonia patients show reduced striatal dopamine D2 receptor (D2R) binding activity. Read More

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Spatially restricted inhibition of cholinergic interneurons in the dorsolateral striatum encourages behavioral exploration.

Eur J Neurosci 2021 Apr 14;53(8):2567-2579. Epub 2021 Feb 14.

Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.

When pursuing desirable outcomes, one must make the decision between exploring possible actions to obtain those outcomes and exploiting known strategies to maximize efficiency. The dorsolateral striatum (DLS) has been extensively studied with respect to how actions can develop into habits and has also been implicated as an area involved in governing exploitative behavior. Surprisingly, prior work has shown that DLS cholinergic interneurons (ChIs) are not involved in the canonical habit formation function ascribed to the DLS but are instead modulators of behavioral flexibility after initial learning. Read More

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Complex effects of eslicarbazepine on inhibitory micro networks in chronic experimental epilepsy.

Epilepsia 2021 02 16;62(2):542-556. Epub 2021 Jan 16.

Medical Faculty, Institute for Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany.

Objective: Many antiseizure drugs (ASDs) act on voltage-dependent sodium channels, and the molecular basis of these effects is well established. In contrast, how ASDs act on the level of neuronal networks is much less understood.

Methods: In the present study, we determined the effects of eslicarbazepine (S-Lic) on different types of inhibitory neurons, as well as inhibitory motifs. Read More

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February 2021