RESUMO
1. The striatum is part of a multisynaptic loop involved in translating higher order cognitive activity into action. The main striatal computational unit is the medium spiny neuron, which integrates inputs arriving from widely distributed cortical neurons and provides the sole striatal output. 2. The membrane potential of medium spiny neurons' displays shifts between a very negative resting state (down state) and depolarizing plateaus (up states) which are driven by the excitatory cortical inputs. 3. Because striatal spiny neurons fire action potentials only during the up state, these plateau depolarizations are perceived as enabling events that allow information processing through cerebral cortex-basal ganglia circuits. In vivo intracellular recording techniques allow to investigate simultaneously the subthreshold behavior of the medium spiny neuron membrane potential (which is a "reading" of distributed patterns of cortical activity) and medium spiny neuron firing (which is an index of striatal output). 4. Recent studies combining intracellular recordings of striatal neurons with field potential recordings of the cerebral cortex illustrate how the analysis of the input-output transformations performed by medium spiny neurons may help to unveil some aspects of information processing in cerebral cortex-basal ganglia circuits, and to understand the origin of the clinical manifestations of Parkinson's disease and other neurologic and neuropsychiatric disorders that result from alterations in dopamine-dependent information processing in the cerebral cortex-basal ganglia circuits.
Assuntos
Relógios Biológicos/fisiologia , Dopamina/metabolismo , Neostriado/metabolismo , Vias Neurais/metabolismo , Neurônios/metabolismo , Potenciais de Ação/fisiologia , Animais , Dendritos/metabolismo , Humanos , Neostriado/citologia , Vias Neurais/citologia , Neurônios/citologia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Transmissão Sináptica/fisiologiaRESUMO
Single unit recordings performed in animal models of Parkinson's disease revealed that output nuclei neurons display modifications in firing pattern and firing rate, which are supposed to give rise to the clinical manifestations of the illness. We examined the activity pattern of single units from the substantia nigra pars reticulata, the main output nuclei of the rodent basal ganglia, in urethane-anesthetized control and 6-hydroxydopamine-lesioned rats (a widespread model of Parkinson's disease). We further studied the effect of a subthalamic nucleus lesion in both experimental groups. Subthalamic nucleus lesion produces behavioral improvement in animal models of Parkinson's disease, and was expected to reverse the changes induced by 6-hydroxydopamine lesions. A meticulous statistical investigation, which included a non-biased classification of the recorded units by means of cluster analysis, allowed us to identify a low frequency oscillation of firing rate ( approximately 0.9 Hz) occurring in approximately 35% of the units recorded from 6-hydroxydopamine-lesioned rats, as the main feature differentiating 6-hydroxydopamine-lesioned and control rats. Subthalamic nucleus lesions significantly reduced the proportion of oscillatory units in 6-hydroxydopamine-lesioned rats. However, the population of nigral units recorded from rats bearing both lesions still differed significantly from control units. These results suggest that oscillatory activity in the basal ganglia output nuclei may be related to some clinical features of parkinsonism, and suggest a putative mechanism through which therapeutic interventions aimed at modifying subthalamic nucleus function produce clinical benefit in Parkinson's disease.
Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos , Vias Neurais/fisiologia , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Substância Negra/fisiologia , Núcleo Subtalâmico/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Caínico/farmacologia , Masculino , Degeneração Neural/induzido quimicamente , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Vias Neurais/citologia , Vias Neurais/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurotoxinas/farmacologia , Oxidopamina/farmacologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley , Substância Negra/citologia , Substância Negra/efeitos dos fármacos , Núcleo Subtalâmico/citologia , Núcleo Subtalâmico/efeitos dos fármacos , Simpatolíticos/farmacologiaRESUMO
Neurons in the basal ganglia output nuclei display rhythmic burst firing after chronic nigrostriatal lesions. The thalamocortical network is a strong endogenous generator of oscillatory activity, and the striatum receives a massive projection from the cerebral cortex. Actually, the membrane potential of striatal projection neurons displays periodic shifts between a very negative resting potential (down state) and depolarizing plateaus (up states) during which they can fire action potentials. We hypothesized that an increased excitability of striatal neurons may allow transmission of cortical slow rhythms through the striatum to the remaining basal ganglia in experimental parkinsonism. In vivo intracellular recordings revealed that striatal projection neurons from rats with chronic nigrostriatal lesions had a more depolarized membrane potential during both the down and up states and an increased firing probability during the up events. Furthermore, lesioned rats had significantly fewer silent neurons than control rats. Simultaneous recordings of the frontal electrocorticogram and membrane potential of striatal projection neurons revealed that the signals were oscillating synchronously in the frequency range 0.4-2 Hz, both in control rats and rats with chronic nigrostriatal lesions. Spreading of the slow cortical rhythm is limited by the very low firing probability of control rat neurons, but a slow oscillation is well reflected in spike trains of approximately 60% of lesioned rat neurons. These findings provide in vivo evidence for a role of dopamine in controlling the flow of cortical activity through the striatum and may be of outstanding relevance for understanding the pathophysiology of Parkinson's disease.