Pre- and Postsynaptic Serotoninergic Excitation of Globus Pallidus Neurons

2008 ◽  
Vol 100 (2) ◽  
pp. 1053-1066 ◽  
Author(s):  
Moshe Rav-Acha ◽  
Hagai Bergman ◽  
Yosef Yarom
Keyword(s):  
Basal Ganglia ◽  
Firing Rate ◽  
Globus Pallidus ◽  
Critical Role ◽  
Brain Slices ◽  
Afferent Input ◽  
Central Nucleus ◽  
Intracellular Recordings ◽  
Current Clamp ◽  
Acid Release

The basal ganglia (BG) play a critical role in the pathogenesis and pathophysiology of Parkinson's disease (PD). Recent studies indicate that serotoninergic systems modulate BG activity and may be implicated in the pathophysiology and treatment of PD. The globus pallidus (GP), the rodent homologue of the primate GPe, is the main central nucleus of the basal ganglia, affecting the striatum, the subthalamic nucleus (STN), and BG output structures. We therefore studied the effect of serotonin (5-HT) and specific 5-HT agonists and antagonists on GP neurons from rat brain slices. Using intra- and extracellular recordings of GP neurons we found that serotonin increases the firing rate of GP neurons. Analyzing the effects of specific 5-HT agonists and antagonists on the firing rate of GP neurons showed that the increase in firing rate is due to the activation of 5-HT1B and 5-HT1A receptors. Intracellular recordings in both voltage- and current-clamp modes revealed that serotonin mediates its effect via pre- and postsynaptic mechanisms. The presynaptic effect is mediated by attenuation of γ-aminobutyric acid release, probably through activation of 5-HT1B receptors. Postsynaptically, serotonin activates a hyperpolarization-activated cation channel, probably via 5-HT1A receptors. Furthermore, serotonin decreases the fast synaptic depression characteristic of the striatal afferent input. The decreased serotonin concentrations in the BG nuclei in PD may contribute to depressed GP activity and enhance the emergence of BG pathological synchronous oscillations. We therefore suggest that future therapeutics of PD should be directed toward restoration of normal serotonin levels in BG nuclei.

Synaptic Regulation of Proopiomelanocortin Neurons Can Occur Distal to the Arcuate Nucleus

2007 ◽  
Vol 97 (5) ◽  
pp. 3298-3304 ◽  
Author(s):  
Shane T. Hentges
Keyword(s):  
Cell Body ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Critical Role ◽  
Brain Slices ◽  
Gaba Release ◽  
Afferent Input ◽  
Inhibitory Synapses ◽  
Body Region ◽  
Neuron Activity

Energy homeostasis is controlled to a large extent by various signals that are integrated in the hypothalamus. It is generally considered that neurons in each of the hypothalamic nuclei are regulated by afferent projections that terminate within the cell body region of the nucleus. However, here it is shown that hypothalamic proopiomelanocortin (POMC) neurons receive synaptic inputs onto distal dendrites that reside outside of the cell body region in the arcuate nucleus. Previous studies using whole cell recordings from identified neurons in brain slices have shown that cannabinoids reduce GABA release from inhibitory synapses onto the POMC cells. Here it was found that endocannabinoids inhibited GABAergic inhibitory postsynaptic currents in POMC neurons only in intact sagittal brain slices, but not coronal, horizontal, or sagittal slices that were truncated rostrally at the level of the optic chiasm. Thus endocannabinoids inhibited presynaptic GABA release only at an anatomically distinct subset of POMC–neuron dendrites that extends rostrally beyond the arcuate nucleus into preoptic hypothalamic regions. There are two key results. First, the activity of POMC neurons can be regulated by afferent input at sites much farther from the soma than previously recognized. Second, endocannabinoids can act to inhibit inputs only at selective dendrites. POMC neurons play a critical role in the maintenance of body weight. Therefore these data suggest that energy balance may be regulated, in part, by modulation of POMC neuron activity at sites outside of the arcuate nucleus.

scholarly journals Multidimensional encoding of movement and contextual variables by rat globus pallidus neurons during a novel environment exposure task

2021 ◽  
Author(s):  
Noam D Peer ◽  
Hagar G Yamin ◽  
Dana Cohen
Keyword(s):  
Globus Pallidus ◽  
Contextual Information ◽  
Critical Role ◽  
Central Nucleus ◽  
Indirect Pathway ◽  
Cognitive Domains ◽  
Novel Environment ◽  
Animal Survival ◽  
Environment Exposure ◽  
Locomotion Speed

The basal ganglia (BG) play a critical role in a variety of functions that are essential for animal survival. Information from different cortical areas propagates through the BG in anatomically segregated circuits along the parallel direct and indirect pathways. We examined how the globus pallidus (GP), a central nucleus within the indirect pathway, encodes input from the motor and cognitive domains. We chronically recorded and analyzed neuronal activity in the GP of rats engaged in a novel environment exposure task. GP neurons displayed multidimensional responses to movement and contextual information. A model predicting single unit activity required many task-related variables, thus confirming the multidimensionality of GP neurons. In addition, populations of GP neurons, but not single units, reliably encoded the animals' locomotion speed and the environmental novelty. We posit that the GP independently processes information from different domains, effectively compresses it and collectively conveys it to successive nuclei.

Auditory response properties of neurons in the putamen and globus pallidus of awake cats

2014 ◽  
Vol 111 (10) ◽  
pp. 2124-2137 ◽  
Author(s):  
Renjia Zhong ◽  
Ling Qin ◽  
Yu Sato
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Afferent Input ◽  
Stimulus Onset ◽  
Natural Sounds ◽  
Response Latencies ◽  
Response Properties ◽  
Response Characteristics ◽  
Auditory Response ◽  
Awake Cats

Several decades of research have provided evidence that the basal ganglia are closely involved in motor processes. Recent clinical, electrophysiological, behavioral data have revealed that the basal ganglia also receive afferent input from the auditory system, but the detailed auditory response characteristics have not yet reported. The present study aimed to reveal the acoustic response properties of neurons in parts of the basal ganglia. We recorded single-unit activities from the putamen (PU) and globus pallidus (GP) of awake cats passively listening to pure tones, click trains, and natural sounds. Our major findings were: 1) responses in both PU and GP neurons were elicited by pure-tone stimuli, whereas PU neurons had lower intensity thresholds, shorter response latencies, shorter excitatory duration, and larger response magnitudes than GP neurons. 2) Some GP neurons showed a suppressive response lasting throughout the stimulus period. 3) Both PU and GP did not follow periodically repeated click stimuli well, and most neurons only showed a phasic response at the stimulus onset and offset. 4) In response to natural sounds, PU also showed a stronger magnitude and shorter duration of excitatory response than GP. The selectivity for natural sounds was low in both nuclei. 5) Nonbiological environmental sounds more efficiently evoked responses in PU and GP than the vocalizations of conspecifics and other species. Our results provide insights into how acoustic signals are processed in the basal ganglia and revealed the distinction of PU and GP in sensory representation.

scholarly journals Effects of Interleukin-1β in Glycinergic Transmission at the Central Amygdala

2021 ◽  
Vol 12 ◽  
Author(s):  
Jocelyn Solorza ◽  
Carolina A. Oliva ◽  
Karen Castillo ◽  
Gabriela Amestica ◽  
María Constanza Maldifassi ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Inhibitory Activity ◽  
Critical Role ◽  
Brain Slices ◽  
Site Directed Mutagenesis ◽  
Interleukin 1Β ◽  
Central Nucleus ◽  
Central Processing ◽  
The Brain ◽  
Glycinergic Neurotransmission

Interleukin-1β (IL-1β) is an important cytokine that modulates peripheral and central pain sensitization at the spinal level. Among its effects, it increases spinal cord excitability by reducing inhibitory Glycinergic and GABAergic neurotransmission. In the brain, IL-1β is released by glial cells in regions associated with pain processing during neuropathic pain. It also has important roles in neuroinflammation and in regulating NMDA receptor activity required for learning and memory. The modulation of glycine-mediated inhibitory activity via IL-1β may play a critical role in the perception of different levels of pain. The central nucleus of the amygdala (CeA) participates in receiving and processing pain information. Interestingly, this nucleus is enriched in the regulatory auxiliary glycine receptor (GlyR) β subunit (βGlyR); however, no studies have evaluated the effect of IL-1β on glycinergic neurotransmission in the brain. Hence, we hypothesized that IL-1β may modulate GlyR-mediated inhibitory activity via interactions with the βGlyR subunit. Our results show that the application of IL-1β (10 ng/ml) to CeA brain slices has a biphasic effect; transiently increases and then reduces sIPSC amplitude of CeA glycinergic currents. Additionally, we performed molecular docking, site-directed mutagenesis, and whole-cell voltage-clamp electrophysiological experiments in HEK cells transfected with GlyRs containing different GlyR subunits. These data indicate that IL-1β modulates GlyR activity by establishing hydrogen bonds with at least one key amino acid residue located in the back of the loop C at the ECD domain of the βGlyR subunit. The present results suggest that IL-1β in the CeA controls glycinergic neurotransmission, possibly via interactions with the βGlyR subunit. This effect could be relevant for understanding how IL-1β released by glia modulates central processing of pain, learning and memory, and is involved in neuroinflammation.

scholarly journals Chemogenetic stimulation of mouse central amygdala corticotropin-releasing factor neurons: Effects on cellular and behavioral correlates of alcohol dependence

2020 ◽  
Author(s):  
Max Kreifeldt ◽  
Melissa A Herman ◽  
Harpreet Sidhu ◽  
Giovana C de Macedo ◽  
Roxana Shahryari ◽  
...  
Keyword(s):  
Alcohol Withdrawal ◽  
Alcohol Intake ◽  
Anterior Commissure ◽  
Critical Role ◽  
Brain Slices ◽  
Receptor Activation ◽  
Corticotropin Releasing Factor ◽  
Central Nucleus ◽  
Crf Neurons ◽  
Stimulation Of

AbstractBackgroundCorticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) plays a critical role in rodent models of excessive alcohol drinking. However, the source of CRF acting in the CeA during alcohol withdrawal remains to be identified. In the present study, we hypothesized that CeA CRF interneurons may represent a behaviorally relevant source of CRF to the CeA increasing motivation for alcohol via negative reinforcement.MethodsWe tested this hypothesis in male mice and used chemogenetics to stimulate CeA CRF neurons in vitro and in vivo.ResultsWe first observed that Crh mRNA expression in the anterior part of the mouse CeA, at the junction with the interstitial nucleus of the posterior limb of the anterior commissure, correlates positively with alcohol intake in C57BL/6J males with a history of chronic binge drinking. We then found that chemogenetic activation of CeA CRF neurons in Crh-IRES-Cre mouse brain slices increases gamma-aminobutyric acid (GABA) release in the medial CeA in part via CRF1 receptor activation, indicating local CRF release. While chemogenetic stimulation of CeA CRF neurons exacerbated novelty-induced feeding suppression, as seen in C57BL/6J males withdrawn from chronic intermittent alcohol inhalation, it had no effect on voluntary alcohol consumption, following either acute or chronic manipulation.ConclusionsAltogether, these findings indicate that hyperactivity of CeA CRF neurons may contribute to elevated CeA GABA levels and negative affect during alcohol withdrawal but is not sufficient to drive alcohol intake escalation in dependent mice.

Serotonergic Inhibition of Action Potential Evoked Calcium Transients in NOS-Containing Mesopontine Cholinergic Neurons

2000 ◽  
Vol 84 (3) ◽  
pp. 1558-1572 ◽  
Author(s):  
Christopher S. Leonard ◽  
Sanjai R. Rao ◽  
Takafumi Inoue
Keyword(s):  
Nitric Oxide ◽  
Firing Rate ◽  
Rem Sleep ◽  
Critical Role ◽  
Brain Slices ◽  
Receptor Activation ◽  
Repetitive Firing ◽  
Dependent Manner ◽  
Laterodorsal Tegmental Nucleus ◽  
State Dependent

Nitric oxide synthase (NOS)-containing mesopontine cholinergic (MPCh) neurons of the laterodorsal tegmental nucleus (LDT) are hypothesized to drive the behavioral states of waking and REM sleep through a tonic increase in firing rate which begins before and is maintained throughout these states. In principle, increased firing could elevate intracellular calcium levels and regulate numerous cellular processes including excitability, gene expression, and the activity of neuronal NOS in a state-dependent manner. We investigated whether repetitive firing, evoked by current injection and N-methyl-d-aspartate (NMDA) receptor activation, produces somatic and proximal dendritic [Ca2+]i transients and whether these transients are modulated by serotonin, a transmitter thought to play a critical role in regulating the state-dependent firing of MPCh neurons. [Ca2+]i was monitored optically from neurons filled with Ca2+ indicators in guinea pig brain slices while measuring membrane potential with sharp microelectrodes or patch pipettes. Neither hyperpolarizing current steps nor subthreshold depolarizing steps altered [Ca2+]i. In contrast, suprathreshold currents caused large and rapid increases in [Ca2+]i that were related to firing rate. TTX (1 μM) strongly attenuated this relation. Addition of tetraethylammonium (TEA, 20 mM), which resulted in Ca2+spiking on depolarization, restored the change in [Ca2+]i to pre-TTX levels. Suprathreshold doses of NMDA also produced increases in [Ca2+]i that were reduced by up to 60% by TTX. Application of 5-HT, which hyperpolarized LDT neurons without detectable changes in [Ca2+]i, suppressed both current- and NMDA-evoked increases in [Ca2+]i by reducing the number of evoked spikes and by inhibiting spike-evoked Ca2+ transients by ∼40% in the soma and proximal dendrites. This inhibition was accompanied by a subtle increase in the spike repolarization rate and a decrease in spike width, as expected for inhibition of high-threshold Ca2+ currents in these neurons. NADPH-diaphorase histochemistry confirmed that recorded cells were NOS-containing. These findings indicate the prime role of action potentials in elevating [Ca2+]i in NOS-containing MPCh neurons. Moreover, they demonstrate that serotonin can inhibit somatic and proximal dendritic [Ca2+]i increases both indirectly by reducing firing rate and directly by decreasing the spike-evoked transients. Functionally, these data suggest that spike-evoked Ca2+ signals in MPCh neurons should be largest during REM sleep when serotonin inputs are expected to be lowest even if equivalent firing rates are reached during waking. Such Ca2+ signals may function to trigger Ca2+-dependent processes including cfosexpression and nitric oxide production in a REM-specific manner.

scholarly journals Striatal Input- and Rate-Dependent Effects of Muscarinic Receptors on Pallidal Firing

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Enrique Querejeta ◽  
Alberto Alatorre ◽  
Alain Ríos ◽  
Rafael Barrientos ◽  
Aldo Oviedo-Chávez ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Firing Rate ◽  
Globus Pallidus ◽  
Muscarinic Receptors ◽  
Spontaneous Firing ◽  
Local Activation ◽  
Rate Dependent ◽  
Ipsilateral Striatum ◽  
Spiking Activity

The globus pallidus (GP) plays a key role in the overall basal ganglia (BG) activity. Despite evidence of cholinergic inputs to GP, their role in the spiking activity of GP neurons has not received attention. We examine the effect of local activation and blockade of muscarinic receptors (MRs) in the spontaneous firing of GP neurons both in normal and ipsilateral striatum-lesioned rats. We found that activation of MRs produces heterogeneous responses in both normal and ipsilateral striatum-lesioned rats: in normal rats the response evoked by MRs depends on the predrug basal firing rate; the inhibition evoked by MRs is higher in normal rats than in striatum-lesioned rats; the number of neurons that undergo inhibition is lower in striatum-lesioned rats than in normal rats. Our data suggest that modulation of MRs in the GP depends on the firing rate before their activation and on the integrity of the striato-pallidal pathway.

scholarly journals The Lamprey Forebrain – Evolutionary Implications

2021 ◽  
pp. 1-16
Author(s):  
Shreyas M. Suryanarayana ◽  
Juan Pérez-Fernández ◽  
Brita Robertson ◽  
Sten Grillner
Keyword(s):  
Basal Ganglia ◽  
Sensory Integration ◽  
Critical Role ◽  
Detailed Comparison ◽  
Common Ancestry ◽  
Dopamine System ◽  
Cortical Areas ◽  
Neural Processes ◽  
Living Group ◽  
Selection Of

The forebrain plays a critical role in a broad range of neural processes encompassing sensory integration and initiation/selection of behaviour. The forebrain functions through an interaction between different cortical areas, the thalamus, the basal ganglia with the dopamine system, and the habenulae. The ambition here is to compare the mammalian forebrain with that of the lamprey representing the oldest now living group of vertebrates, by a review of earlier studies. We show that the lamprey dorsal pallium has a motor, a somatosensory, and a visual area with retinotopic representation. The lamprey pallium was previously thought to be largely olfactory. There is also a detailed similarity between the lamprey and mammals with regard to other forebrain structures like the basal ganglia in which the general organisation, connectivity, transmitters and their receptors, neuropeptides, and expression of ion channels are virtually identical. These initially unexpected results allow for the possibility that many aspects of the basic design of the vertebrate forebrain had evolved before the lamprey diverged from the evolutionary line leading to mammals. Based on a detailed comparison between the mammalian forebrain and that of the lamprey and with due consideration of data from other vertebrate groups, we propose a compelling account of a pan-vertebrate schema for basic forebrain structures, suggesting a common ancestry of over half a billion years of vertebrate evolution.

scholarly journals Morphological Abnormalities in the Basal Ganglia of Dystonia Patients

2021 ◽  
pp. 1-12
Author(s):  
Xi Bai ◽  
Peter Vajkoczy ◽  
Katharina Faust
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Trajectory Planning ◽  
Matched Control ◽  
Young Patients ◽  
Control Population ◽  
Pathogenic Role ◽  
Target Region ◽  
Morphological Abnormalities ◽  
Primary Dystonia

<b><i>Objective:</i></b> The pathophysiology of dystonia is poorly understood. As opposed to secondary forms of dystonia, primary dystonia has long been believed to lack any neuroanatomical substrate. During trajectory planning for DBS, however, conspicuous T2-hyperinstensive signal alterations (SA) were registered within the target region, even in young patients, where ischemia is rare. <b><i>Methods:</i></b> Fifty MRIs of primary dystonia patients scheduled for DBS were analyzed. Total basal ganglia (BG) volumes, as well as proportionate SA volumes, were measured and compared to 50 age-matched control patients. <b><i>Results:</i></b> There was a 10-fold preponderance of percentaged SA within the globus pallidus (GP) in dystonia patients. The greatest disparity was in young patients &#x3c;25 years. Also, total BG volume differences were observed with larger GP and markedly smaller putamen and caudate in the dystonia group. <b><i>Conclusions:</i></b> BG morphology in primary dystonia differed from a control population. Volume reductions of the putamen and caudate may reflect functional degeneration, while volume increases of the GP may indicate overactivity. T2-hyperintensive SA in the GP of young primary dystonia patients, where microvascular lesions are highly unlikely, are striking. Their pathogenic role remains unclear.

Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to Sonic Hedgehog

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5079-5089 ◽  
Author(s):  
J.D. Kohtz ◽  
D.P. Baker ◽  
G. Corte ◽  
G. Fishell
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Sonic Hedgehog ◽  
Adult Brain ◽  
Ganglionic Eminence ◽  
Lateral Ganglionic Eminence ◽  
Expression Characteristic ◽  
Sonic Hedgehog Gene ◽  
Embryonic Structure ◽  
Sequential Induction

The cortex and basal ganglia are the major structures of the adult brain derived from the embryonic telencephalon. Two morphologically distinct regions of the basal ganglia are evident within the mature ventral telencephalon, the globus pallidus medially, and the striatum, which is positioned between the globus pallidus and the cortex. Deletion of the Sonic Hedgehog gene in mice indicates that this secreted signaling molecule is vital for the generation of both these ventral telencephalic regions. Previous experiments showed that Sonic Hedgehog induces differentiation of ventral neurons characteristic of the medial ganglionic eminence, the embryonic structure which gives rise to the globus pallidus. In this paper, we show that later in development, Sonic Hedgehog induces ventral neurons with patterns of gene expression characteristic of the lateral ganglionic eminence. This is the embryonic structure from which the striatum is derived. These results suggest that temporally regulated changes in Sonic Hedgehog responsiveness are integral in the sequential induction of basal telencephalic structures.

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