Abstract
RationaleCorticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues.ObjectivesHere, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats.MethodsThe 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively.ResultsWe found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field.ConclusionsThese results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control.
Highlights
Adapting to changing environments requires the allocation of attentional resources including inhibition of inappropriate responding to allow efficient goal-directed behaviour
These results complement previous lesion work in which the dorsomedial striatum (DMS) and orbitofrontal cortex were implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control
DMS lesions increase premature and perseverative responding, reflecting deficits in impulsivity and compulsivity, respectively (Rogers et al 2001). In line with these inhibitory deficits, lesions of the orbitofrontal cortex (OFC) (Chudasama et al 2003), an area which projects to the DMS in a topographic manner (Schilman et al 2008), increase perseverative responses in the 5CSRTT. This parallels the effects of OFC and DMS lesions in reversal learning tasks, which result in an increase in perseverative responses after
Summary
Adapting to changing environments requires the allocation of attentional resources including inhibition of inappropriate responding to allow efficient goal-directed behaviour. These functions have traditionally been associated with the corticostriatal network; emerging evidence suggests that corticostriatal inputs are subject to thalamic modulation in the striatum (Bradfield et al 2013a, b). DMS lesions increase premature and perseverative responding, reflecting deficits in impulsivity and compulsivity, respectively (Rogers et al 2001) In line with these inhibitory deficits, lesions of the orbitofrontal cortex (OFC) (Chudasama et al 2003), an area which projects to the DMS in a topographic manner (Schilman et al 2008), increase perseverative responses in the 5CSRTT. This parallels the effects of OFC and DMS lesions in reversal learning tasks, which result in an increase in perseverative responses after
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