Abstract
BackgroundCerebellar cortical molecular layer interneurons (MLIs) play essential roles in sensory information processing by the cerebellar cortex. However, recent experimental and modeling results are questioning traditional roles for molecular layer inhibition in the cerebellum.Methods and Main ResultsSynaptic responses of MLIs and Purkinje cells (PCs), evoked by air-puff stimulation of the ipsilateral whisker pad were recorded from cerebellar cortex Crus II in urethane-anesthetized ICR mice by in vivo whole-cell patch-clamp recording techniques. Under current-clamp (I = 0), air-puff stimuli were found to primarily produce inhibition in PCs. In MLIs, this stimulus evoked spike firing regardless of whether they made basket-type synaptic connections or not. However, MLIs not making basket-type synaptic connections had higher rates of background activity and also generated spontaneous spike-lets. Under voltage-clamp conditions, excitatory postsynaptic currents (EPSCs) were recorded in MLIs, although the predominant response of recorded PCs was an inhibitory postsynaptic potential (IPSP). The latencies of EPSCs were similar for all MLIs, but the time course and amplitude of EPSCs varied with depth in the molecular layer. The highest amplitude, shortest duration EPSCs were recorded from MLIs deep in the molecular layer, which also made basket-type synaptic connections. Comparing MLI to PC responses, time to peak of PC IPSP was significantly slower than MLI recorded EPSCs. Blocking GABAA receptors uncovered larger EPSCs in PCs whose time to peak, half-width and 10–90% rising time were also significantly slower than in MLIs. Biocytin labeling indicated that the MLIs (but not PCs) are dye-coupled.ConclusionsThese findings indicate that tactile face stimulation evokes rapid excitation in MLIs and inhibition occurring at later latencies in PCs in mouse cerebellar cortex Crus II. These results support previous suggestions that the lack of parallel fiber driven PC activity is due to the effect of MLI inhibition.
Highlights
Purkinje cells (PCs) are the most investigated neurons in the mammalian cerebellum
These findings indicate that tactile face stimulation evokes rapid excitation in molecular layer interneurons (MLIs) and inhibition occurring at later latencies in PCs in mouse cerebellar cortex Crus II
These results support previous suggestions that the lack of parallel fiber driven PC activity is due to the effect of MLI inhibition
Summary
Purkinje cells (PCs) are the most investigated neurons in the mammalian cerebellum. Their unique discharge of two distinct types of spike firing patterns, simple spikes and complex spikes, enables their positive identification under in vivo recording conditions. More natural stimulation of afferent cerebellar cortical activation failed to produce ‘‘beam-like’’ excitation of PCs [3,4,5,6,7]. Our results support the proposal that the molecular layer inhibitory interneurons play a complex, subtle and perhaps more central role in PC responses to afferent input and in the physiological and functional organization of the cerebellar cortex. Recent experimental and modeling results are questioning traditional roles for molecular layer inhibition in the cerebellum
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