Presynaptic modulation by somatostatin in the rat neostriatum is altered in a model of parkinsonism

2012 ◽  
Vol 108 (4) ◽  
pp. 1032-1043 ◽  
Author(s):  
Violeta G. López-Huerta ◽  
Eduardo Blanco-Hernández ◽  
José Bargas ◽  
Elvira Galarraga
Keyword(s):  
Presynaptic Inhibition ◽  
Feedback Inhibition ◽  
Cell Voltage ◽  
Inhibitory Synapses ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Presynaptic Modulation ◽  
Inhibitory Circuit ◽  
6 Hydroxydopamine ◽  
Presynaptic Facilitation

Somatostatin (SST) is a peptide synthesized and released by a class of neostriatal local GABAergic interneurons, which, to some extent, are in charge of the feedforward inhibitory circuit. Spiny projection neurons (SPNs) make synapses with each other via their local axon collaterals, shaping the feedback inhibitory circuit. Both inhibitory circuits, feedforward and feedback, are related through SST, which, being released by interneurons, presynaptically inhibits connections among SPNs. Here, we studied SST presynaptic modulation of synapses among SPNs in the 6-hydroxydopamine (6-OHDA) rodent model of parkinsonism. We performed antidromic field stimulation from the external globus pallidus and whole cell voltage-clamp recordings of antidromically evoked inhibitory postsynaptic currents (IPSCs) among SPNs. SST presynaptically reduced IPSCs by ∼34% in all control synapses tested. However, after striatal dopamine deprivation, three changes became evident. First, it was harder to evoke feedback inhibition. Second, presynaptic inhibition of some SPNs connections was larger than in controls: 57% reduction in ∼53% of evoked IPSCs. Presynaptic inhibition was recorded from direct pathway neurons (direct SPNs). Finally, SST also induced presynaptic facilitation in some SPNs connections, with 82% enhancement in ∼43% of evoked IPSCs. Presynaptic facilitation was recorded from indirect pathway neurons (indirect SPNs). Both inhibition and facilitation were accompanied by corresponding changes in the paired pulse ratio. It was demonstrated that after dopamine deprivation, SST modulation is altered in surviving feedback inhibitory synapses. It may underlie a homeostatic mechanism trying to compensate for the excitability imbalance between direct and indirect basal ganglia pathways found during parkinsonism.

scholarly journals Diverse Short-Term Dynamics of Inhibitory Synapses Converging on Striatal Projection Neurons: Differential Changes in a Rodent Model of Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Janet Barroso-Flores ◽  
Marco A. Herrera-Valdez ◽  
Violeta Gisselle Lopez-Huerta ◽  
Elvira Galarraga ◽  
José Bargas
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Voltage ◽  
Rodent Model ◽  
Inhibitory Synapses ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Dopamine Depletion ◽  
Short Term ◽  
6 Hydroxydopamine

Most neurons in the striatum are projection neurons (SPNs) which make synapses with each other within distances of approximately 100 µm. About 5% of striatal neurons are GABAergic interneurons whose axons expand hundreds of microns. Short-term synaptic plasticity (STSP) between fast-spiking (FS) interneurons and SPNs and between SPNs has been described with electrophysiological and optogenetic techniques. It is difficult to obtain pair recordings from some classes of interneurons and due to limitations of actual techniques, no other types of STSP have been described on SPNs. Diverse STSPs may reflect differences in presynaptic release machineries. Therefore, we focused the present work on answering two questions: Are there different identifiable classes of STSP between GABAergic synapses on SPNs? And, if so, are synapses exhibiting different classes of STSP differentially affected by dopamine depletion? Whole-cell voltage-clamp recordings on SPNs revealed three classes of STSPs: depressing, facilitating, and biphasic (facilitating-depressing), in response to stimulation trains at 20 Hz, in a constant ionic environment. We then used the 6-hydroxydopamine (6-OHDA) rodent model of Parkinson’s disease to show that synapses with different STSPs are differentially affected by dopamine depletion. We propose a general model of STSP that fits all the dynamics found in our recordings.

scholarly journals Parallel Movement-suppressing Striatal Output Pathways

2020 ◽  
Author(s):  
Qiaoling Cui ◽  
Xixun Du ◽  
Isaac Y. M. Chang ◽  
Arin Pamukcu ◽  
Varoth Lilascharoen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Body Movement ◽  
Disease Model ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Striatal Projection Neurons ◽  
6 Hydroxydopamine

AbstractThe classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and how they are involved in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting role of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+ neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+ projection was dramatically strengthened. As DLSdSPN-Npas1+ projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opponent output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes plastic changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.

Upregulation of D2-class signaling in dopamine-denervated striatum is in part mediated by D3 receptors acting on CaV2.1 channels via PIP2 depletion

2011 ◽  
Vol 105 (5) ◽  
pp. 2260-2274 ◽  
Author(s):  
G. Aleph Prieto ◽  
Azucena Perez-Burgos ◽  
Marcela Palomero-Rivero ◽  
Elvira Galarraga ◽  
Rene Drucker-Colin ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Intracellular Signaling ◽  
Cell Voltage ◽  
Gaba Release ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Dopamine Depletion ◽  
R And D ◽  
Relative Contribution ◽  
6 Hydroxydopamine

The loss of dopaminergic neurons in the substantia nigra compacta followed by striatal dopamine depletion is a hallmark of Parkinson's disease. After dopamine depletion, dopaminergic D2 receptor (D2R)-class supersensitivity develops in striatal neurons. The supersensitivity results in an enhanced modulation of Ca2+ currents by D2R-class receptors. However, the relative contribution of D2R, D3R, and D4R types to the supersensitivity, as well as the mechanisms involved, have not been elucidated. In this study, whole cell voltage-clamp recordings were performed to study Ca2+ current modulation in acutely dissociated striatal neurons obtained from rodents with unilateral 6-hydroxydopamine lesions in the substantia nigra compacta. Selective antagonists for D2R, D3R, and D4R types were used to identify whether the modulation by one of these receptors experiences a selective change after dopaminergic denervation. It was found that D3R-mediated modulation was particularly enhanced. Increased modulation targeted CaV2.1 (P/Q) Ca2+ channels via the depletion of phosphatidylinositol 4,5-bisphosphate, an intracellular signaling cascade hard to detect in control neurons and hypothesized as being amplified by dopamine depletion. An imbalance in the striatal expression of D3R and its splice variant, D3nf, accompanied enhanced D3R activity. Because CaV2.1 Ca2+ channels mediate synaptic GABA release from the terminals of striatal neurons, reinforcement of their inhibition by D3R may explain in part the profound decrease in synaptic strength in the connections among striatal projection neurons observed in the dopamine-depleted striatum.

Bursting in Substantia Nigra Pars Reticulata Neurons In Vitro: Possible Relevance for Parkinson Disease

2007 ◽  
Vol 98 (4) ◽  
pp. 2311-2323 ◽  
Author(s):  
Osvaldo Ibáñez-Sandoval ◽  
Luis Carrillo-Reid ◽  
Elvira Galarraga ◽  
Dagoberto Tapia ◽  
Ernesto Mendoza ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Temporal Structure ◽  
Projection Neurons ◽  
Rate Model ◽  
Indirect Pathway ◽  
Bath Application ◽  
Pattern Generators ◽  
Oscillatory Model

Projection neurons of the substantia nigra reticulata (SNr) convey basal ganglia (BG) processing to thalamocortical and brain stem circuits responsible for movement. Two models try to explain pathological BG performance during Parkinson disease (PD): the rate model, which posits an overexcitation of SNr neurons due to hyperactivity in the indirect pathway and hypoactivity of the direct pathway, and the oscillatory model, which explains PD as the product of pathological pattern generators disclosed by dopamine reduction. These models are, apparently, incompatible. We tested the predictions of the rate model by increasing the excitatory drive and reducing the inhibition on SNr neurons in vitro. This was done pharmacologically with bath application of glutamate agonist N-methyl-d-aspartate and GABAA receptor blockers, respectively. Both maneuvers induced bursting behavior in SNr neurons. Therefore synaptic changes forecasted by the rate model induce the electrical behavior predicted by the oscillatory model. In addition, we found evidence that CaV3.2 Ca2+ channels are a critical step in generating the bursting firing pattern in SNr neurons. Other ion channels involved are: hyperpolarization-activated cation channels, high-voltage-activated Ca2+ channels, and Ca2+-activated K+ channels. However, although these channels shape the temporal structure of bursting, only CaV3.2 Ca2+ channels are indispensable for the initiation of the bursting pattern.

Different Inhibitory Inputs Onto Neostriatal Projection Neurons as Revealed by Field Stimulation

2005 ◽  
Vol 93 (2) ◽  
pp. 1119-1126 ◽  
Author(s):  
Fatuel Tecuapetla ◽  
Luis Carrillo-Reid ◽  
Jaime N. Guzmán ◽  
Elvira Galarraga ◽  
José Bargas
Keyword(s):  
Channel Blocker ◽  
Inhibitory Synapses ◽  
Projection Neurons ◽  
Medium Spiny Neurons ◽  
Field Stimulation ◽  
Paired Pulse ◽  
Postsynaptic Currents ◽  
Spiny Neurons ◽  
Short Time ◽  
Paired Pulse Depression

This work investigated if diverse properties could be ascribed to evoked inhibitory postsynaptic currents (IPSCs) recorded on rat neostriatal neurons when field stimulation was delivered at two different locations: the globus pallidus (GP) and the neostriatum (NS). Previous work stated that stimulation in the GP could antidromically excite projection axons from medium spiny neurons. This maneuver would predominantly activate the inhibitory synapses that interconnect spiny cells. In contrast, intrastriatal stimulation would preferentially activate inhibitory synapses provided by interneurons. This study shows that, in fact, intensity-amplitude experiments are able to reveal different properties for IPSCs evoked from these two locations (GP and NS). In addition, while all IPSCs evoked from the GP were always sensitive to ω-conotoxin GVIA (CaV2.22.2 or N-channel blocker), one-half of the inhibition evoked from the NS exhibited little sensitivity to ω-conotoxin GVIA. Characteristically, all ω-conotoxin GVIA–insensitive IPSCs exhibited strong paired pulse depression, whereas ω-conotoxin GVIA–sensitive IPSCs evoked from either the GP or the NS could exhibit short-time depression or facilitation. ω-Agatoxin TK (CaV2.12.1+ or P/Q-channel blocker) blocked IPSCs evoked from both locations. Therefore 1) distinct inhibitory inputs onto projection neostriatal cells can be differentially stimulated with field electrodes; 2) N-type Ca2+ channels are not equally expressed in inhibitory terminals activated in the NS; and 3) synapses that interconnect spiny neurons use both N- and P/Q-type Ca2+ channels.

scholarly journals Retinal Synaptic Pathways Underlying the Response of the Rabbit Local Edge Detector

2010 ◽  
Vol 103 (5) ◽  
pp. 2757-2769 ◽  
Author(s):  
Thomas L. Russell ◽  
Frank S. Werblin
Keyword(s):  
Feedback Inhibition ◽  
Receptive Fields ◽  
Cell Voltage ◽  
Retinal Ganglion ◽  
Edge Detector ◽  
Temporal Properties ◽  
Field Sensitivity ◽  
Glycinergic Inhibition ◽  
Local Edge ◽  
Feedforward Inhibition

We studied the circuitry that underlies the behavior of the local edge detector (LED) retinal ganglion cell in rabbit by measuring the spatial and temporal properties of excitatory and inhibitory currents under whole cell voltage clamp. Previous work showed that LED excitation is suppressed by activity in the surround. However, the contributions of outer and inner retina to this characteristic and the neurotransmitters used are currently unknown. Blockage of retinal inhibitory pathways (GABAA, GABAC, and glycine) eliminated edge selectivity. Inverting gratings in the surround with 50-μm stripe sizes did not stimulate horizontal cells, but suppressed on and off excitation by roughly 60%, indicating inhibition of bipolar terminals (feedback inhibition). On pharmacologic blockage, we showed that feedback inhibition used both GABAA and GABAC receptors, but not glycine. Glycinergic inhibition suppressed GABAergic feedback inhibition in the center, enabling larger excitatory currents in response to luminance changes. Excitation, feedback inhibition, and direct (feedforward) inhibition responded to luminance-neutral flipping gratings of 20- to 50-μm widths, showing they are driven by independent subunits within their receptive fields, which confers sensitivity to borders between areas of texture and nontexture. Feedforward inhibition was glycinergic, its rise time was faster than decay time, and did not function to delay spiking at the onset of a stimulus. Both the on and off phases could be triggered by luminance shifts as short in duration as 33 ms and could be triggered during scenes that already produced a high baseline level of feedforward inhibition. Our results show how LED circuitry can use subreceptive field sensitivity to detect visual edges via the interaction between excitation and feedback inhibition and also respond to rapid luminance shifts within a rapidly changing scene by producing feedforward inhibition.

scholarly journals Control of Basal Ganglia Output by Direct and Indirect Pathway Projection Neurons

2013 ◽  
Vol 33 (47) ◽  
pp. 18531-18539 ◽  
Author(s):  
B. S. Freeze ◽  
A. V. Kravitz ◽  
N. Hammack ◽  
J. D. Berke ◽  
A. C. Kreitzer
Keyword(s):  
Basal Ganglia ◽  
Projection Neurons ◽  
Indirect Pathway

Visualization of zebrafish striatum direct and indirect pathway projection neurons

2011 ◽  
Vol 71 ◽  
pp. e372
Author(s):  
Ryo Aoki ◽  
Tazu Aoki ◽  
Masakazu Agetsuma ◽  
Toshiyuki Shiraki ◽  
Takashi Tsuboi ◽  
...  
Keyword(s):  
Projection Neurons ◽  
Indirect Pathway

scholarly journals Short-term plasticity in glomerular inhibitory circuits shapes olfactory bulb output

2020 ◽  
Vol 123 (3) ◽  
pp. 1120-1132 ◽  
Author(s):  
Fu-Wen Zhou ◽  
Zuo-Yi Shao ◽  
Michael T. Shipley ◽  
Adam C. Puche
Keyword(s):  
Fluorescent Protein ◽  
Feedback Inhibition ◽  
Olfactory Nerve ◽  
Inhibitory Synapses ◽  
Acid Decarboxylase ◽  
Short Term ◽  
Short Term Plasticity ◽  
Inhibitory Circuits ◽  
Frequency Independent ◽  
Green Fluorescent

Short-term plasticity is a fundamental synaptic property thought to underlie memory and neural processing. The glomerular microcircuit comprises complex excitatory and inhibitory interactions and transmits olfactory nerve signals to the excitatory output neurons, mitral/tufted cells (M/TCs). The major glomerular inhibitory interneurons, short axon cells (SACs) and periglomerular cells (PGCs), both provide feedforward and feedback inhibition to M/TCs and have reciprocal inhibitory synapses between each other. Olfactory input is episodically driven by sniffing. We hypothesized that frequency-dependent short-term plasticity within these inhibitory circuits could influence signals sent to higher-order olfactory networks. To assess short-term plasticity in glomerular circuits and MC outputs, we virally delivered channelrhodopsin-2 (ChR2) in glutamic acid decarboxylase-65 promotor (GAD2-cre) or tyrosine hydroxylase promoter (TH-cre) mice and selectively activated one of these two populations while recording from cells of the other population or from MCs. Selective activation of TH-ChR2-expressing SACs inhibited all recorded GAD2-green fluorescent protein(GFP)-expressing presumptive PGC cells, and activation of GAD2-ChR2 cells inhibited TH-GFP-expressing SACs, indicating reciprocal inhibitory connections. SAC synaptic inhibition of GAD2-expressing cells was significantly facilitated at 5–10 Hz activation frequencies. In contrast, GAD2-ChR2 cell inhibition of TH-expressing cells was activation-frequency independent. Both SAC and PGC inhibition of MCs also exhibited short-term plasticity, pronounced in the 5–20 Hz range corresponding to investigative sniffing frequency ranges. In paired SAC and olfactory nerve electrical stimulations, the SAC to MC synapse was able to markedly suppress MC spiking. These data suggest that short-term plasticity across investigative sniffing ranges may differentially regulate intra- and interglomerular inhibitory circuits to dynamically shape glomerular output signals to downstream targets. NEW & NOTEWORTHY Short-term plasticity is a fundamental synaptic property that modulates synaptic strength based on preceding activity of the synapse. In rodent olfaction, sensory input arrives episodically driven by sniffing rates ranging from quiescent respiration (1–2 Hz) through to investigative sniffing (5–10 Hz). Here we show that glomerular inhibitory networks are exquisitely sensitive to input frequencies and exhibit plasticity proportional to investigative sniffing frequencies. This indicates that olfactory glomerular circuits are dynamically modulated by episodic sniffing input.

Sign in / Sign up

Export Citation Format

Share Document