Abstract
The striatum is the major input structure of basal ganglia and is involved in adaptive control of behaviour through the selection of relevant informations. Dopaminergic neurons that innervate striatum die in Parkinson disease, leading to inefficient adaptive behaviour. Neuronal activity of striatal medium spiny neurons (MSN) is modulated by dopamine receptors. Although dopamine signalling had received substantial attention, consequences of dopamine depletion on MSN intrinsic excitability remain unclear. Here we show, by performing perforated patch clamp recordings on brain slices, that dopamine depletion leads to an increase in MSN intrinsic excitability through the decrease of an inactivating A-type potassium current, I A. Despite the large decrease in their excitatory synaptic inputs determined by the decreased dendritic spines density and the increase in minimal current to evoke the first EPSP, this increase in intrinsic excitability resulted in an enhanced responsiveness to their remaining synapses, allowing them to fire similarly or more efficiently following input stimulation than in control condition. Therefore, this increase in intrinsic excitability through the regulation of I A represents a form of homeostatic plasticity allowing neurons to compensate for perturbations in synaptic transmission and to promote stability in firing. The present observations show that this homeostatic ability to maintain firing rates within functional range also occurs in pathological conditions, allowing stabilizing neural computation within affected neuronal networks.
Highlights
The striatum, the major input structure of basal ganglia, is involved in adaptive control of behaviour through the selection of behaviourally relevant information [1] and is important for the control of movements and the motivational, cognitive and emotional aspects of motor activity
Validation of the reserpine/alpha-methyl-p-tyrosine (AMPT) treatment induction of dopamine depletion in young rats As stated in the introduction, the consequences of dopamine receptors activation on striatal neurons physiology have been the subject of numerous studies, the alterations of medium-size spiny neurons (MSN) intrinsic excitability resulting from dopamine depletion remain incompletely documented
We showed that dopamine depletion leads to an increase in MSN intrinsic excitability both in a reserpinetreatment induced dopamine depletion and in a 6-OHDA induced degeneration of dopaminergic neurons
Summary
The striatum, the major input structure of basal ganglia, is involved in adaptive control of behaviour through the selection of behaviourally relevant information [1] and is important for the control of movements and the motivational, cognitive and emotional aspects of motor activity. MSN occupy a strategic integrative position since these cortical inputs converge with dopaminergic afferents from the substantia nigra pars compacta and the ventral tegmental area that tightly regulate their activity The involvement of this nigrostriatal dopaminergic pathway in Parkinson’s disease, being subject to neurodegeneration, and in drug addiction, demonstrates its pivotal function in striatal physiology. The putative existence and the nature of a homeostatic response of these neurons in case of dopamine depletion have been recently suggested [7], they were never experimentally examined This could be highly relevant since it has been demonstrated in a variety of physiological conditions such as memory storage or activity-dependent development that the average neuronal activity levels are maintained by homeostatic plasticity mechanisms that adjust synaptic strengths and/or intrinsic excitability to promote stability [8,9,10]. The existence of homeostatic plasticity and its nature in pathological conditions are mostly unknown
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