Intrastriatal excitotoxic lesion or dopamine depletion of the neostriatum differentially impairs response execution in extrapersonal space

Abstract

Dysfunction of the neostriatum, a primary feature of several neurodegenerative disorders, including Parkinson's disease and Huntington's disease, has been found to result in impaired localisation of, and reaction to, contralateral stimuli. On the basis of previous findings, it is hypothesised that, with increasing eccentricity of the response option, striatal cell loss may impair response localisation at the furthest levels of eccentricity, whereas dopamine (DA) depletion may not impact adversely upon responses executed in this extrapersonal space. In order to elucidate more fully the function of the striatum, the present study examined the differential impact of unilateral DA depletion or excitoxic lesion on response execution in ipsilateral and contralateral space at up to four levels of eccentricity. The results confirmed that, after both types of striatal dysfunction, the sensory ability to detect stimuli remains intact, whereas the ability to direct responses in absolute contralateral space is impaired. Distinct differences in the profiles of impairment were, however, evident, with a marked increase in response omissions observed after DA depletion, which may reflect decreased motivational processing, and recovery of function observed in rats with excitotoxic lesions, which suggests the ability to re-learn. Furthermore, the data demonstrate that, after cell loss, responding in near contralateral space is controlled by competing striata, whereas responding in extrapersonal space relies on the contralateral hemisphere. These results have implications for understanding the role of the striatum in egocentrically defined response localisation, as well as for unravelling the behavioural impact of striatal cell loss or aberrant DA transmission observed in neurodegenerative diseases.

A Longitudinal Operant Assessment of Cognitive and Behavioural Changes in the HdhQ111 Mouse Model of Huntington’s Disease

“…It could also be that motor dysfunction prevents animals from responding to the S1 SILT stimulus accurately. Although, the deficits observed in the SILT task in S2 accuracy among Hdh Q111/+ animals may be attributed to motor problems, these deficits may further be explained by the eccentricity of response required in this task, which has been previously demonstrated in rats with striatal lesions [ 57 ].…”

Impaired cognitive and motor function are coincident with l-DOPA-induced dyskinesia in a model of Parkinson’s disease

“…It was suggested, therefore, that lesioned rats presented with an impairment in encoding responses in egocentric space, which may have manifested due to a distortion in the representation of response space 16 . More recently, it has been suggested that this impairment in spatial encoding may also interact with a motivational dysfunction, potentially influenced by loss of DA along the VTA-nucleus accumbens pathway, which together influence the ability to respond in this lateralised task 8 , 17 .…”

The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats

“…Dopamine was beneficial for the recovery of ischemic stroke, especially the recovery of motor function, learning and memory, and cognitive function (Kaushik et al, 2020). However, it has been suggested that sustained autoxidation of dopamine could lead to an excessive accumulation of toxic quinones and cytotoxic free radicals, which would be detrimental to stroke recovery (Lelos et al, 2012).…”