scholarly journals Direct pathway neurons in mouse dorsolateral striatum in vivo receive stronger synaptic input than indirect pathway neurons

2019 ◽  
Vol 122 (6) ◽  
pp. 2294-2303 ◽  
Author(s):  
Marko Filipović ◽  
Maya Ketzef ◽  
Ramon Reig ◽  
Ad Aertsen ◽  
Gilad Silberberg ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Basal Ganglia ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Potential Fluctuations ◽  
Direct Pathway ◽  
Spiny Neurons ◽  
Total Input ◽  
Membrane Potential Fluctuations

Striatal projection neurons, the medium spiny neurons (MSNs), play a crucial role in various motor and cognitive functions. MSNs express either D1- or D2-type dopamine receptors and initiate the direct-pathway (dMSNs) or indirect pathways (iMSNs) of the basal ganglia, respectively. dMSNs have been shown to receive more inhibition than iMSNs from intrastriatal sources. Based on these findings, computational modeling of the striatal network has predicted that under healthy conditions dMSNs should receive more total input than iMSNs. To test this prediction, we analyzed in vivo whole cell recordings from dMSNs and iMSNs in healthy and dopamine-depleted (6OHDA) anaesthetized mice. By comparing their membrane potential fluctuations, we found that dMSNs exhibited considerably larger membrane potential fluctuations over a wide frequency range. Furthermore, by comparing the spike-triggered average membrane potentials, we found that dMSNs depolarized toward the spike threshold significantly faster than iMSNs did. Together, these findings (in particular the STA analysis) corroborate the theoretical prediction that direct-pathway MSNs receive stronger total input than indirect-pathway neurons. Finally, we found that dopamine-depleted mice exhibited no difference between the membrane potential fluctuations of dMSNs and iMSNs. These data provide new insights into the question of how the lack of dopamine may lead to behavioral deficits associated with Parkinson’s disease. NEW & NOTEWORTHY The direct and indirect pathways of the basal ganglia originate from the D1- and D2-type dopamine receptor expressing medium spiny neurons (dMSNs and iMSNs). Theoretical results have predicted that dMSNs should receive stronger synaptic input than iMSNs. Using in vivo intracellular membrane potential data, we provide evidence that dMSNs indeed receive stronger input than iMSNs, as has been predicted by the computational model.

scholarly journals Direct Pathway Neurons in Mouse Dorsolateral Striatum In Vivo Receive Stronger Synaptic Input than Indirect Pathway Neurons

2019 ◽  
Author(s):  
Marko Filipović ◽  
Maya Ketzef ◽  
Ramon Reig ◽  
Ad Aertsen ◽  
Gilad Silberberg ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Synaptic Input ◽  
Excitatory Input ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Potential Fluctuations ◽  
Direct Pathway ◽  
Spiny Neurons ◽  
Membrane Potential Fluctuations

AbstractStriatal projection neurons, the medium spiny neurons (MSNs), play a crucial role in various motor and cognitive functions. MSNs express either D1 or D2 type dopamine receptors and initiate the direct-pathway (dMSNs) or indirect pathways (iMSNs) of the basal ganglia, respectively. dMSNs have been shown to receive more inhibition than iMSNs from intrastriatal sources. Based on these findings, computational modelling of the striatal network has predicted that under healthy conditions dMSNs should receive more excitatory input than iMSNs. To test this prediction, we analyzed in vivo whole-cell recordings from dMSNs and iMSNs in healthy and dopamine-depleted (6OHDA) anaesthetized mice. By comparing their membrane potential fluctuations, we found that dMSNs exhibited considerably larger membrane potential fluctuations over a wide frequency range. Furthermore, by comparing the spike-triggered average membrane potentials, we found that dMSNs depolarized towards the spike threshold significantly faster than iMSNs did. Together, these finding corroborate the theoretical prediction that direct-pathway MSNs receive stronger input than indirect-pathway neurons. Finally, we found that dopamine-depleted mice exhibited no difference between the membrane potential fluctuations of dMSNs and iMSNs. These data provide new insights into the question how a lack of dopamine may lead to behavior deficits associated with Parkinson’s disease.Significance statementThe direct and indirect pathways of the basal ganglia originate from the D1 and D2 type dopamine receptor expressing medium spiny neurons (dMSNs and iMSNs), respectively. To understand the role of the striatum in brain function and dysfunction it is important to characterize the differences in synaptic inputs to the two MSN types. Theoretical results predicted that dMSNs should receive stronger excitatory input than iMSNs. Here, we studied membrane potential fluctuation statistics of MSNs recorded in vivo in anaesthetized mice and found that dMSNs, indeed, received stronger synaptic input than iMSNs. We corroborated this finding by spike-triggered membrane potential analysis, showing that dMSNs spiking required more synaptic input than iMSNs spiking did, as had been predicted by computational models.

#3101 Imbalanced basal ganglia connectivity is associated with motor deficits and apathy in Huntingtons disease: first evidence from human in vivo neuroimaging

2021 ◽  
Vol 92 (8) ◽  
pp. A6.1-A6
Author(s):  
Akshay Nair ◽  
Adeel Razi ◽  
Sarah Gregory ◽  
Robb Rutledge ◽  
Geraint Rees ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Bayesian Model ◽  
Empirical Bayes ◽  
Model Comparison ◽  
De Novo ◽  
Effective Connectivity ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Bayesian Model Comparison

BackgroundThe gating of movement in humans is thought to depend on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways the direct and indirect pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is to encourage and inhibit movement respectively. In Huntingtons disease (HD), the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition that gives rise to the characteristic motor features of the condition. But early HD is also specifically associated with apathy, a failure to engage in goal-directed movement. We hypothesised that in HD, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction respectively.MethodsUsing a novel technique for estimating dynamic effective connectivity of the basal ganglia, we tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal HD (n = 94). We used spectral dynamic casual modelling of resting state fMRI data to model effective connectivity in a model of these cortico-striatal pathways. We used an advanced approach at the group level by combining Parametric Empirical Bayes and Bayesian Model Reduction procedure to generate large number of competing models and compare them by using Bayesian model comparison.ResultsWith this fully Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. Firstly, more severe motor signs in HD were associated with altered connectivity in the indirect pathway and by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component of our model.ConclusionsThe empirical evidence we provide here is the first in vivo demonstration that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of HD and may have important implications for therapeutics.

Spontaneous Subthreshold Membrane Potential Fluctuations and Action Potential Variability of Rat Corticostriatal and Striatal Neurons In Vivo

1997 ◽  
Vol 77 (4) ◽  
pp. 1697-1715 ◽  
Author(s):  
Edward A. Stern ◽  
Anthony E. Kincaid ◽  
Charles J. Wilson
Keyword(s):  
Membrane Potential ◽  
Synaptic Input ◽  
High Frequency ◽  
Action Potentials ◽  
State Transitions ◽  
Striatal Neurons ◽  
Interspike Intervals ◽  
Potential Fluctuations ◽  
Membrane Potential Fluctuations

Stern, Edward A., Anthony E. Kincaid, and Charles J. Wilson. Spontaneous subthreshold membrane potential fluctuations and action potential variability of rat corticostriatal and striatal neurons in vivo. J. Neurophysiol. 77: 1697–1715, 1997. We measured the timing of spontaneous membrane potential fluctuations and action potentials of medial and lateral agranular corticostriatal and striatal neurons with the use of in vivo intracellular recordings in urethan-anesthetized rats. All neurons showed spontaneous subthreshold membrane potential shifts from 7 to 32 mV in amplitude, fluctuating between a hyperpolarized down state and depolarized up state. Action potentials arose only during the up state. The membrane potential state transitions showed a weak periodicity with a peak frequency near 1 Hz. The peak of the frequency spectra was broad in all neurons, indicating that the membrane potential fluctuations were not dominated by a single periodic function. At frequencies >1 Hz, the log of magnitude decreased linearly with the log of frequency in all neurons. No serial dependence was found for up and down state durations, or for the time between successive up or down state transitions, showing that the up and down state transitions are not due to superimposition of noisy inputs onto a single frequency. Monte Carlo simulations of stochastic synaptic inputs to a uniform finite cylinder showed that the Fourier spectra obtained for corticostriatal and striatal neurons are inconsistent with a Poisson-like synaptic input, demonstrating that the up state is not due to an increase in the strength of an unpatterned synaptic input. Frequency components arising from state transitions were separated from those arising from the smaller membrane potential fluctuations within each state. A larger proportion of the total signal was represented by the fluctuations within states, especially in the up state, than was predicted by the simulations. The individual state spectra did not correspond to those of random synaptic inputs, but reproduced the spectra of the up and down state transitions. This suggests that the process causing the state transitions and the process responsible for synaptic input may be the same. A high-frequency periodic component in the up states was found in the majority of the corticostriatal cells in the sample. The average size of the component was not different between neurons injected with QX-314 and control neurons. The high-frequency component was not seen in any of our sample of striatal cells. Corticostriatal and striatal neurons' coefficients of variation of interspike intervals ranged from 1.0 to 1.9. When interspike intervals including a down state were subtracted from the calculation, the coefficient of variation ranged from 0.4 to 1.1, indicating that a substantial proportion of spike interval variance was due to the subthreshold membrane potential fluctuations.

scholarly journals Direct and Indirect Pathway Neurons in Ventrolateral Striatum Differentially Regulate Licking Movement and Nigral Responses

2021 ◽  
Author(s):  
Zhaorong Chen ◽  
Zhi-Yu Zhang ◽  
Taorong Xie ◽  
Wen Zhang ◽  
Yaping Li ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Rate Increase ◽  
Drinking Behavior ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Related Activity ◽  
Tongue Protrusion ◽  
D1 And D2 Receptors ◽  
Spiny Neurons ◽  
Output Neurons

SUMMARYDrinking behavior in rodents is characterized by stereotyped, rhythmic licking movement, which is regulated by the basal ganglia. It is unclear how direct and indirect pathways control the lick bout and individual lick event. We find that inactivating D1 and D2 receptors-expressing medium spiny neurons (MSNs) in the ventrolateral striatum (VLS) oppositely alters the number of licks in a bout. D1- and D2-MSNs exhibit similar patterns of lick sequence-related activity but different phases of oscillation time-locked to the lick cycle. On timescale of a lick cycle, transient inactivation of D1-MSNs during tongue protrusion reduces lick probability, whereas transient inactivation of D2-MSNs has no effect. On timescale of a lick bout, inactivation of D1-MSNs (D2-MSNs) causes rate increase (decrease) in a subset of basal ganglia output neurons that decrease firing during licking. Our results reveal the distinct roles of D1- and D2-MSNs in regulating licking at both coarse and fine timescales.

scholarly journals Dendritic Voltage and Calcium-Gated Channels Amplify the Variability of Postsynaptic Responses in a Purkinje Cell Model

1998 ◽  
Vol 80 (2) ◽  
pp. 504-519 ◽  
Author(s):  
Erik De Schutter
Keyword(s):  
Membrane Potential ◽  
Purkinje Cell ◽  
Cell Model ◽  
Excitatory Postsynaptic Potential ◽  
Potential Fluctuations ◽  
Active Dendrites ◽  
Somatic Response ◽  
Background Input ◽  
Membrane Potential Fluctuations

De Schutter, Erik. Dendritic voltage and calcium-gated channels amplify the variability of postsynaptic responses in a Purkinje cell model. J. Neurophysiol. 80: 504–519, 1998. The dendrites of most neurons express several types of voltage and Ca2+-gated channels. These ionic channels can be activated by subthreshold synaptic input, but the functional role of such activations in vivo is unclear. The interaction between dendritic channels and synaptic background input as it occurs in vivo was studied in a realistic computer model of a cerebellar Purkinje cell. It previously was shown using this model that dendritic Ca2+ channels amplify the somatic response to synchronous excitatory inputs. In this study, it is shown that dendritic ion channels also increased the somatic membrane potential fluctuations generated by the background input. This amplification caused a highly variable somatic excitatory postsynaptic potential (EPSP) in response to a synchronous excitatory input. The variability scaled with the size of the response in the model with excitable dendrite, resulting in an almost constant coefficient of variation, whereas in a passive model the membrane potential fluctuations simply added onto the EPSP. Although the EPSP amplitude in the active dendrite model was quite variable for different patterns of background input, it was insensitive to changes in the timing of the synchronous input by a few milliseconds. This effect was explained by slow changes in dendritic excitability. This excitability was determined by how the background input affected the dendritic membrane potentials in the preceding 10–20 ms, causing changes in activation of voltage and Ca2+-gated channels. The most important model variables determining the excitability at the time of a synchronous input were the Ca2+-activation of K+ channels and the inhibitory synaptic conductance, although many other model variables could be influential for particular background patterns. Experimental evidence for the amplification of postsynaptic variability by active dendrites is discussed. The amplification of the variability of EPSPs has important functional consequences in general and for cerebellar Purkinje cells specifically. Subthreshold, background input has a much larger effect on the responses to coherent input of neurons with active dendrites compared with passive dendrites because it can change the effective threshold for firing. This gives neurons with dendritic calcium channels an increased information processing capacity and provides the Purkinje cell with a gating function.

scholarly journals Medium spiny neurons activity reveals the discrete segregation of mouse dorsal striatum

2020 ◽  
Author(s):  
J. Alegre-Cortés ◽  
M. Sáez ◽  
R. Montanari ◽  
R. Reig
Keyword(s):  
Basal Ganglia ◽  
Dorsal Striatum ◽  
Medium Spiny Neurons ◽  
Extracellular Recordings ◽  
Electrophysiological Properties ◽  
Spiny Neurons ◽  
Sensory Activity ◽  
Fast Oscillations ◽  
Anatomical Evidence

AbstractBehavioural studies differentiate the rodent dorsal striatum (DS) into lateral and medial regions; however, anatomical evidence suggests that it is a unified structure. To understand striatal dynamics and basal ganglia functions, it is essential to clarify the circuitry that supports this behavioural-based segregation. Here, we show that the mouse DS is made of two non-overlapping functional circuits divided by a boundary. Combining in vivo optopatch-clamp and extracellular recordings of spontaneous and evoked sensory activity, we demonstrate different coupling of lateral and medial striatum to the cortex together with an independent integration of the spontaneous activity, due to particular corticostriatal connectivity and local attributes of each region. Additionally, we show differences in slow and fast oscillations and in the electrophysiological properties between striatonigral and striatopallidal neurons. In summary, these results demonstrate that the rodent DS is segregated in two neuronal circuits, in homology with the caudate and putamen nuclei of primates.

scholarly journals Stochastic Emergence of Repeating Cortical Motifs in Spontaneous Membrane Potential Fluctuations In Vivo

Neuron ◽  
2007 ◽  
Vol 53 (3) ◽  
pp. 413-425 ◽  
Author(s):  
Alik Mokeichev ◽  
Michael Okun ◽  
Omri Barak ◽  
Yonatan Katz ◽  
Ohad Ben-Shahar ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potential Fluctuations ◽  
Membrane Potential Fluctuations
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