scholarly journals Pauses in cholinergic interneuron firing exert an inhibitory control on striatal output in vivo

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Stefano Zucca ◽  
Aya Zucca ◽  
Takashi Nakano ◽  
Sho Aoki ◽  
Jeffery Wickens
Keyword(s):  
Membrane Potential ◽  
Projection Neurons ◽  
Tonic Firing ◽  
Short Term Plasticity ◽  
Cholinergic Interneurons ◽  
Significant Events ◽  
Output Neurons ◽  
Potential Activity ◽  
Membrane Potential Fluctuations

The cholinergic interneurons (CINs) of the striatum are crucial for normal motor and behavioral functions of the basal ganglia. Striatal CINs exhibit tonic firing punctuated by distinct pauses. Pauses occur in response to motivationally significant events, but their function is unknown. Here we investigated the effects of pauses in CIN firing on spiny projection neurons (SPNs) – the output neurons of the striatum – using in vivo whole cell and juxtacellular recordings in mice. We found that optogenetically-induced pauses in CIN firing inhibited subthreshold membrane potential activity and decreased firing of SPNs. During pauses, SPN membrane potential fluctuations became more hyperpolarized and UP state durations became shorter. In addition, short-term plasticity of corticostriatal inputs was decreased during pauses. Our results indicate that, in vivo, the net effect of the pause in CIN firing on SPNs activity is inhibition and provide a novel mechanism for cholinergic control of striatal output.

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.

Microcircuits of the Striatum

2017 ◽  
pp. 121-132
Author(s):  
Natalie M. Doig ◽  
J. Paul Bolam
Keyword(s):  
Basal Ganglia ◽  
Caudate Nucleus ◽  
Internal Capsule ◽  
Projection Neurons ◽  
Gabaergic Interneurons ◽  
Cholinergic Interneurons ◽  
Spiny Neurons ◽  
Output Neurons ◽  
Major Division ◽  
Selection Of

The striatum (or caudate-putamen, or caudate nucleus and putamen in those species in which they are divided by the internal capsule) is the major division of the basal ganglia, a group of structures involved in a variety of processes, including movement and cognitive and mnemonic functions. The striatum consists of a population of principal neurons, the medium-sized, densely spiny neurons (MSNs)—accounting for up to 97% of all neurons depending on species—which are the projection neurons of the striatum, several populations of GABAergic interneurons, and a population of cholinergic interneurons. The principal afferents of the striatum are glutamatergic, are derived from the cortex and thalamus, and mainly innervate the spines of MSNs. The essential computation performed by the striatum is the decision about which MSNs will fire, the consequence of which is altered firing of basal ganglia output neurons, and hence the selection of the basal ganglia–associated behavior.

scholarly journals Regulation of Action-Potential Firing in Spiny Neurons of the Rat Neostriatum In Vivo

1998 ◽  
Vol 79 (5) ◽  
pp. 2358-2364 ◽  
Author(s):  
J. R. Wickens ◽  
C. J. Wilson
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Action Potentials ◽  
Projection Neurons ◽  
Excitatory Postsynaptic Potential ◽  
Action Potential Firing ◽  
Current Pulses ◽  
Spiny Neurons ◽  
Potential Firing

Wickens, J. R. and C. J. Wilson. Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo. J. Neurophysiol. 79: 2358–2364, 1998. Both silent and spontaneously firing spiny projection neurons have been described in the neostriatum, but the reason for their differences in firing activity are unknown. We compared properties of spontaneously firing and silent spiny neurons in urethan-anesthetized rats. Neurons were identified as spiny projection neurons after labeling by intracellular injection of biocytin. The threshold for action-potential firing was measured under three different conditions: 1) electrical stimulation of the contralateral cerebral cortex, 2) brief directly applied current pulses, and 3) spontaneous action-potentials occurring during spontaneous episodes of depolarization (up state). The average membrane potential and the amplitude of noiselike fluctuations of membrane potential in the up state were determined by fitting a Gaussian curve to the membrane-potential distribution. All neurons in the sample exhibited spontaneous membrane potential shifts between a hyperpolarized down state and a depolarized up state, but not all fired action potentials while in the up state. The difference between the spontaneously firing and the silent spiny neurons was in the average membrane potential in the up state, which was significantly more depolarized in the spontaneously firing than in the silent spiny neurons. There were no significant differences in the threshold, the amplitude of the noiselike fluctuations of membrane potential in the up state, or in the proportion of time that the membrane potential was in the up state. In both spontaneously firing and silent neurons, the threshold for action potentials evoked by current pulses was significantly higher than for those evoked by cortical stimulation. Application of more intense current pulses that reproduced the excitatory postsynaptic potential rate of rise produced firing at correspondingly lower thresholds. Because the membrane potential in the up state is mainly determined by the balance between the synaptic drive and the outward potassium conductances activated in the subthreshold range of membrane potentials, either or both of these factors may determine whether firing occurs in response to spontaneous afferent activity.

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 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 Inhibition of cholinergic interneurons potentiates corticostriatal transmission in D1 receptor-expressing medium-sized spiny neurons and restores motor learning in parkinsonian condition

2021 ◽  
Author(s):  
Gwenaelle Laverne ◽  
Jonathan Pesce ◽  
Ana Reynders ◽  
Christophe Melon ◽  
Lydia Kerkerian-Le Goff ◽  
...  
Keyword(s):  
Motor Learning ◽  
Long Term Potentiation ◽  
D1 Receptor ◽  
Skill Learning ◽  
D1 Receptors ◽  
Projection Neurons ◽  
Cholinergic Interneurons ◽  
Term Potentiation ◽  
The Impact

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson′s disease. How this signal regulates the functioning of the striatum remains an open question. To address this issue, we examined the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium-sized spiny projection neurons expressing dopamine D1 receptors (D1 MSNs). Brief interruption of CIN activity had no effect in control condition whereas it increased glutamatergic responses in D1 MSNs after nigrostriatal dopamine denervation. This potentiation was dependent upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by opto/chemogenetic strategies in vivo rescued long-term potentiation in some MSNs and alleviated motor learning deficits in parkinsonian mice. Taken together, our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.

scholarly journals Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum

2019 ◽  
Author(s):  
Yan-Feng Zhang ◽  
Simon D. Fisher ◽  
Manfred Oswald ◽  
Jeffery R. Wickens ◽  
John N. J. Reynolds
Keyword(s):  
Synaptic Plasticity ◽  
Reinforcement Learning ◽  
Long Term Potentiation ◽  
Dopamine Neurons ◽  
Projection Neurons ◽  
Cholinergic Interneurons ◽  
Term Potentiation ◽  
Phasic Activation

AbstractPauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.

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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