scholarly journals Differential Synaptic Input to External Globus Pallidus Neuronal Subpopulations In Vivo

2020 ◽  
Author(s):  
Maya Ketzef ◽  
Gilad Silberberg
Keyword(s):  
Globus Pallidus ◽  
Synaptic Input ◽  
Membrane Properties ◽  
Projection Neurons ◽  
Inhibitory Input ◽  
Indirect Pathway ◽  
Functional Roles ◽  
Striatal Projection Neurons ◽  
Afferent Inputs

SummaryThe rodent external Globus Pallidus (GPe) contains two main neuronal subpopulations, prototypic and arkypallidal cells, which differ in their cellular properties. Their functional synaptic connectivity is, however, largely unknown. Here, we studied the membrane properties and synaptic inputs to these subpopulations in the mouse GPe. We obtained in vivo whole-cell recordings from identified GPe neurons and used optogenetic stimulation to dissect their afferent inputs from the striatum and subthalamic nucleus (STN). All GPe neurons received barrages of excitatory and inhibitory input during slow wave activity. The modulation of their activity was cell-type specific and shaped by their respective membrane properties and afferent inputs. Both GPe subpopulations received synaptic input from STN and striatal projection neurons (MSNs). STN and indirect pathway MSNs strongly targeted prototypic cells while direct pathway MSNs selectively inhibited arkypallidal cells. We show that GPe subtypes are differently embedded in the basal ganglia network, supporting distinct functional roles.

scholarly journals Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Farid N Garas ◽  
Rahul S Shah ◽  
Eszter Kormann ◽  
Natalie M Doig ◽  
Federica Vinciati ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Form And Function ◽  
Cortical Oscillations ◽  
Striatal Projection Neurons ◽  
Distinct Cell ◽  
And Function ◽  
Two Populations

Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping striatal output. Schemes of basal ganglia circuit dynamics generally consider striatal PV+ interneurons to be homogenous, despite considerable heterogeneity in both form and function. We demonstrate that the selective co-expression of another calcium-binding protein, secretagogin (Scgn), separates PV+ interneurons in rat and primate striatum into two topographically-, physiologically- and structurally-distinct cell populations. In rats, these two interneuron populations differed in their firing rates, patterns and relationships with cortical oscillations in vivo. Moreover, the axons of identified PV+/Scgn+ interneurons preferentially targeted the somata of SPNs of the so-called ‘direct pathway’, whereas PV+/Scgn- interneurons preferentially targeted ‘indirect pathway’ SPNs. These two populations of interneurons could therefore provide a substrate through which either of the striatal output pathways can be rapidly and selectively inhibited to subsequently mediate the expression of behavioral routines.

Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex

2020 ◽  
Author(s):  
Simon Weiler ◽  
Drago Guggiana Nilo ◽  
Tobias Bonhoeffer ◽  
Mark Hübener ◽  
Tobias Rose ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Synaptic Input ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Orientation Tuning ◽  
Inhibitory Input ◽  
Layer 2 ◽  
Dendritic Complexity ◽  
Inhibitory Synaptic Input

AbstractNeocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs with in vivo 2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS).Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PC in vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.

Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method

2014 ◽  
Vol 112 (1) ◽  
pp. 120-146 ◽  
Author(s):  
Kenji Morita
Keyword(s):  
D2 Receptor ◽  
Computational Method ◽  
Cortical Activation ◽  
Projection Neurons ◽  
Indirect Pathway ◽  
Short Term ◽  
Apparent Contradiction ◽  
Striatal Projection Neurons ◽  
Cortical Inputs ◽  
Stimulation Of

The corticostriatal system is considered to be crucially involved in learning and action selection. Anatomical studies have shown that two types of corticostriatal neurons, intratelencephalic (IT) and pyramidal tract (PT) cells, preferentially project to dopamine D1 or D2 receptor-expressing striatal projection neurons, respectively. In contrast, an optogenetic study has shown that stimulation of IT axons evokes comparable responses in D1 and D2 cells and that stimulation of PT axons evokes larger responses in D1 cells. Since the optogenetic study applied brief stimulation only, however, the overall impacts of repetitive inputs remain unclear. Moreover, the apparent contradiction between the anatomical and optogenetic results remains to be resolved. I addressed these issues by using a computational approach. Specifically, I constructed a model of striatal response to cortical inputs, with parameters regarding short-term synaptic plasticity and anatomical connection strength for each connection type. Under the constraint of the optogenetic results, I then explored the parameters that best explain the previously reported paired-pulse ratio of response in D1 and D2 cells to cortical and intrastriatal stimulations, which presumably recruit different compositions of IT and PT fibers. The results indicate that 1) IT→D1 and PT→D2 connections are anatomically stronger than IT→D2 and PT→D1 connections, respectively, consistent with the previous findings, and that 2) IT→D1 and PT→D2 synapses entail short-term facilitation, whereas IT→D2 and PT→D1 synapses would basically show depression, and thereby 3) repetitive IT or PT inputs have larger overall impacts on D1 or D2 cells, respectively, supporting a recently proposed hypothesis on the roles of corticostriatal circuits in reinforcement learning.

scholarly journals A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations

2017 ◽  
Vol 37 (41) ◽  
pp. 9977-9998 ◽  
Author(s):  
Andrew Sharott ◽  
Federica Vinciati ◽  
Kouichi C. Nakamura ◽  
Peter J. Magill
Keyword(s):  
Projection Neurons ◽  
Indirect Pathway ◽  
Beta Oscillations ◽  
Striatal Projection Neurons

scholarly journals Dopamine modulates the size of striatal projection neuron ensembles

2019 ◽  
Author(s):  
Marta Maltese ◽  
Jeffrey R. March ◽  
Alexander G. Bashaw ◽  
Nicolas X. Tritsch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Voluntary Movements ◽  
Indirect Pathway ◽  
Two Photon ◽  
Direct Pathway ◽  
Brain Circuits

SUMMARYDopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca2+ imaging to simultaneously monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that, contrary to prevailing models, DA does not modulate activity rates in either pathway strongly or differentially. Instead, DA exerts a prominent influence on the overall number of direct and indirect pathway SPNs recruited during behavior. Chronic loss of midbrain DA neurons in a model of Parkinson’s disease selectively impacts direct pathway ensembles and profoundly alters how they respond to DA elevation. Our results indicate that DA regulates striatal output by dynamically reconfiguring its sparse ensemble code and provide novel insights into the pathophysiology of Parkinson’s disease.

scholarly journals PO-147 Effect of Exercise-induced Fatigue on the Electrical Activity of the External Globus Pallidus Neurons in rats

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Hao Yu ◽  
Lijuan Hou ◽  
Jing Ma ◽  
Zhifeng Wang ◽  
Gang Zhao ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Globus Pallidus ◽  
Low Frequency ◽  
Extracellular Recording ◽  
Central Fatigue ◽  
Control Group ◽  
Indirect Pathway ◽  
Exercise Induced ◽  
Exercise Fatigue

Objective The motor cortex (MC) stimulation-induced unitary responses of globus pallidus external segment (GPe) neurons in control and exercise induced-fatigue rats were recorded in vivo to examine the role of cortical-striatum-external globus pallidal pathway in the mechanism of central fatigue. Methods 32 Clean healthy male Wistar rats (260~300g), were randomly divided into 4 groups: control group (Control), 1-day fatigue group (1FG), 3-day fatigue group (3FG) and 7-day fatigue group (7FG). Rats were subjected to a 5-day adaptive treadmill training. Modified Bedford treadmill exercise with progressively increasing load was used to creat the exercise fatigue model. （3 levels:8.2 m/min, 15 min; 15m/min, 15 min; 20 m/min, lasting till exhaustion） The spontaneous unit activity and responses to MC stimulation of GPe neurons were recorded by the electrophysiological technique of extracellular recording of glass microelectrodes. Results The results showed that the firing frequency of high-frequency firing with pause (HFP) and low frequency firing with burst (LFB) in the GPe of 1FG was comparable with that of control group (P>0.05). However in 3FG and 7FG , the percentage of HFP neuron was significantly decreased (P<0.05), while the proportion of LFB was significantly increased (P<0.05), and the average firing rate of LFB was higher and inter spike intervals (ISI) was significantly lower than that of the control group. With 200μA electrical stimulation, the explosive discharge of GPe neurons was attenuated after fatigue in rats. The response of GPe neurons to variable frequency stimulation in exhausted model groups was stronger than that of the control group.MC-stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GPe neurons. The population of neurons showing a short inhibition slightly increased in 3FG and 7FG. Conclusions 1. The results confirmed that GPe is an important nucleus of basal ganglia involved in the regulation of exercise-induced fatigue by the change of spontaneous activity. Electrical stimulation on the cortex can alter response patterns of GPe neurons in exercise-induced fatigue rats, the results confirmed that the Ctx-Str-GPe neural pathway is involved in the regulation of exercise fatigue, and the indirect pathway is over-activated.

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.

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