Synaptic currents in cerebellar Purkinje cells.

Abstract

Cerebellar Purkinje cells are known to receive strong excitatory input from two major pathways originating outside the cerebellum and inhibitory input from two types of neurons in the cerebellar cortex. The functions and synaptic strengths of these pathways are only partially known. We have used the patch-clamp technique applied to Purkinje cells in thin slices of rat cerebellum to measure directly the postsynaptic currents arising from the two major excitatory pathways and one of the inhibitory inputs. Inhibitory synaptic currents occur spontaneously with high frequency and are variable in amplitude, ranging, in our recording conditions with'high internal Cl-, from less than 100 pA to more than 1 nA. These currents are blocked by the y-aminobutyrate type A antagonist bicuculline. One of the excitatory inputs is all or none. For threshold stimulation, the synaptic current is either full amplitude, when the presynaptic fiber is successfully stimulated, or completely absent. This synaptic current is often larger than 1 nA and is virtually eliminated by 2 ImM 6-cyano-7-nitroquinoxaline-2,3-dione, a blocking agent thought to be specific for glutamate receptors that are not of the N-methyl-D-aspartate type. Its all-or-none character identifies it as arising from a climbing-fiber synapse. The other excitatory input produces a synaptic current that is smoothly graded as a function of stimulus intensity. This response we believe arises from the stimulation of mossy fibers or granule cells. The synaptic current associated with this input is also 'largely eliminated by 2 ImM 6-cyano-7-nitroquinoxaline-2,3-dione.A useful new technique (1) Fig. lA (2, 3). The first of these relays information arising from sensory receptors in all parts of the body to the cerebellum, by way of mossy fibers. In mature animals, a mossy fiber makes contact with several hundred granule cells, each of which gives rise to a parallel fiber. The parallel fibers ascend through the molecular layer, bifurcate, and synapse with Purkinje cells. Each Purkinje cell receives synaptic input from as many as 80,000 parallel fibers. The path thus is from mossy fibers to granule cells to Purkinje cells. The second input, the climbing-fiber input, is strikingly different. A Purkinje cell receives input from a single climbing fiber, and transmission in this pathway is one to one. The functional significance of these two inputs is not yet certain. An interesting hypothesis holds that a climbing fiber serves as "instructor" to alter the strength of parallel fiber synapses (4,5).In addition to the excitatory inputs there are two inhibitory inputs, the more powerful being from basket cells. A Purkinje cell receives input from numerous basket cells.The changes in Purkinje cell membrane potential that follow activation ofthe excitatory inputs have been described in vivo and in cerebellar slices (3). We report here observations on the postsynaptic currents elicited by (i) climbing fibers, (ii) a second excitatory pathway probably involving mossy and parallel fibe...

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