Cortical and Thalamic Excitation Mediate the Multiphasic Responses of Striatal Cholinergic Interneurons to Motivationally Salient Stimuli

Doig, Natalie M.; Magill, Peter J.; Apicella, Paul; Bolam, J. Paul; Sharott, Andrew

doi:10.1523/jneurosci.4627-13.2014

Cited by 119 publications

(160 citation statements)

References 55 publications

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“…Glutamatergic pyramidal neurons in the cerebral cortex also innervate striatal ChIs (Lapper and Bolam, 1992; Sidibe and Smith, 1999; Thomas et al, 2000; Ding et al, 2010; Doig et al, 2014; Kosillo et al, 2016). To determine if corticostriatal synapses on ChIs were affected by mHtt, Q175 mice were crossed with a transgenic mouse expressing ChR2 throughout the cerebral cortex (Arenkiel et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…Both anatomical (Lapper and Bolam, 1992) and physiological (Ding et al, 2010; Threlfell et al, 2012; Doig et al, 2014) evidence suggests that although they receive cortical glutamatergic input, the intralaminar nuclei (ILN) of the thalamus provide the predominant source of extrinsic excitatory input to ChIs (Sidibe and Smith, 1999; Ding et al, 2010). This feature of ChIs might be critical to the pathophysiology of HD.…”

Section: Introductionmentioning

confidence: 99%

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Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease

Tanimura

Lim

Buendía

et al. 2016

Front. Syst. Neurosci.

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Huntington’s disease (HD) is a neurodegenerative disorder characterized by deficits in movement control that are widely viewed as stemming from pathophysiological changes in the striatum. Giant, aspiny cholinergic interneurons (ChIs) are key elements in the striatal circuitry controlling movement, but whether their physiological properties are intact in the HD brain is unclear. To address this issue, the synaptic properties of ChIs were examined using optogenetic approaches in the Q175 mouse model of HD. In ex vivo brain slices, synaptic facilitation at thalamostriatal synapses onto ChIs was reduced in Q175 mice. The alteration in thalamostriatal transmission was paralleled by an increased response to optogenetic stimulation of cortical axons, enabling these inputs to more readily induce burst-pause patterns of activity in ChIs. This adaptation was dependent upon amplification of cortically evoked responses by a post-synaptic upregulation of voltage-dependent Na+ channels. This upregulation also led to an increased ability of somatic spikes to invade ChI dendrites. However, there was not an alteration in the basal pacemaking rate of ChIs, possibly due to increased availability of Kv4 channels. Thus, there is a functional “re-wiring” of the striatal networks in Q175 mice, which results in greater cortical control of phasic ChI activity, which is widely thought to shape the impact of salient stimuli on striatal action selection.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease

Tanimura

Lim

Buendía

et al. 2016

Front. Syst. Neurosci.

View full text Add to dashboard Cite

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“…These signals are likely generated as a result of experience-dependent plasticity in the circuits that form the input -output networks of this large region of the basal ganglia. This includes cholinergic interneurons (Doig et al 2014). It is likely that through these and other network activities, including processing through the thalamus and neocortex and their projections to the striatum, neurons in the striatum build up selective responses to particular environmental events and certain behavioral actions and contexts.…”

Section: Reinforcement-based Learning Represents a Core Mechanism Thomentioning

confidence: 99%

The Striatum: Where Skills and Habits Meet

Graybiel

Grafton

2015

Cold Spring Harb Perspect Biol

372

305

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After more than a century of work concentrating on the motor functions of the basal ganglia, new ideas have emerged, suggesting that the basal ganglia also have major functions in relation to learning habits and acquiring motor skills. We review the evidence supporting the role of the striatum in optimizing behavior by refining action selection and in shaping habits and skills as a modulator of motor repertoires. These findings challenge the notion that striatal learning processes are limited to the motor domain. The learning mechanisms supported by striatal circuitry generalize to other domains, including cognitive skills and emotion-related patterns of action.T he nuclei and interconnections of the basal ganglia are widely recognized for modulating motor behavior. Whether measured at the neuronal or regional level, the activities of neurons in the basal ganglia correlate with many movement parameters, particularly those that influence the vigor of an action, such as force and velocity. Pathology within different basal ganglia circuits predictably leads to either hypokinetic or hyperkinetic movement disorders. In parallel, however, the basal ganglia, and especially the striatum, are now widely recognized as being engaged in activity related to learning. Interactions between the dopamine-containing neurons of the midbrain and their targets in the striatum are critical to this function. A fundamental question is how these two capacities-(motor behavior and reinforcement-based learning)-relate to each other and what role the striatum and other basal ganglia nuclei have in forming new behavioral repertoires. Here, we consider relevant physiological properties of the striatum by contrasting two common forms of adaptation found in all mammals: the acquisition of behavioral habits and physical skills.Without resorting to technical definitions, we all have an intuition of what habits and skills are. Tying one's shoes after putting them on is something we consider a habit-part of a behavioral routine. The capacity to tie the laces properly is a skill. Habits and skills have many common features. Habits are consistent behavEditors: Eric R. Kandel, Yadin Dudai, and Mark R. Mayford Additional Perspectives on Learning and Memory available at

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“…With exposure to behaviorally relevant stimuli or reward, most cholinergic interneurons respond with a brief pause in firing of approximately 200 to 300 milliseconds duration, which may be preceded or followed by increased firing rates [114]. Excitatory cortical and thalamic inputs appear to play a role in initiating pause-excitation events that follow reward-predicting stimuli [115]. Pauses are associated with increases in firing by midbrain dopaminergic neurons [116].…”

Section: A Threshold Model For Cholinergic Effects On Reinforced Behamentioning

confidence: 99%

A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders

Grasing

2016

Behavioural Brain Research

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The cholinergic system plays important roles in both learning and addiction. Medications that modify cholinergic tone can have pronounced effects on behaviors reinforced by natural and drug reinforcers. Importantly, enhancing the action of acetylcholine (ACh) in the nucleus accumbens and ventral tegmental area (VTA) dopamine system can either augment or diminish these behaviors. A threshold model is presented that can explain these seemingly contradictory results. Relatively low levels of ACh rise above a lower threshold, facilitating behaviors supported by drugs or natural reinforcers. Further increases in cholinergic tone that rise above a second upper threshold oppose the same behaviors. Accordingly, cholinesterase inhibitors, or agonists for nicotinic or muscarinic receptors, each have the potential to produce biphasic effects on reward behaviors. Pretreatment with either nicotinic or muscarinic antagonists can block drug- or food- reinforced behavior by maintaining cholinergic tone below its lower threshold. Potential threshold mediators include desensitization of nicotinic receptors and biphasic effects of ACh on the firing of medium spiny neurons. Nicotinic receptors with high- and low-affinity appear to play greater roles in reward enhancement and inhibition, respectively. Cholinergic inhibition of natural and drug rewards may serve as mediators of previously described opponent processes. Future studies should evaluate cholinergic agents across a broader range of doses, and include a variety of reinforced behaviors.

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Cortical and Thalamic Excitation Mediate the Multiphasic Responses of Striatal Cholinergic Interneurons to Motivationally Salient Stimuli

Cited by 119 publications

References 55 publications

Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease

Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington’s Disease

The Striatum: Where Skills and Habits Meet

A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders

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