Proliferation of External Globus Pallidus-Subthalamic Nucleus Synapses following Degeneration of Midbrain Dopamine Neurons

摘要: The symptoms of Parkinson's disease (PD) are related to changes in the frequency and pattern activity reciprocally connected GABAergic external globus pallidus (GPe) glutamatergic subthalamic nucleus (STN). In idiopathic experimental PD, GPe STN exhibit hypoactivity hyperactivity, respectively, abnormal synchronous rhythmic burst firing. Following lesion midbrain dopamine neurons, emerges slowly intensifies gradually until it stabilizes after 2-3 weeks. Alterations cellular/network properties may therefore underlie expression Because powerfully regulates frequency, pattern, synchronization activity, electrophysiological, molecular, anatomical measures GPe-STN transmission were compared control 6-hydroxydopamine-lesioned rats mice. depletion: (1) (but not amplitude) mIPSCs increased by ∼70%; (2) amplitude evoked IPSCs isoguvacine-evoked current ∼60% ∼70%, respectively; (3) mRNA encoding α1, β2, γ2 GABA(A) receptor subunits 15-30%; (4) density postsynaptic gephyrin subunit coimmunoreactive structures ∼40%, whereas vesicular GABA transporter bassoon axon terminals was unchanged; (5) number ultrastructurally defined synapses per terminal doubled with no alteration terminal/synapse size or target preference. Thus, loss leads, through an increase synaptic connections terminal, substantial strengthening pathway. This adaptation oppose hyperactivity but could also contribute firing patterns parkinsonian STN.