Synaptic modification of parallel fibre‐Purkinje cell transmission in in vitro guinea‐pig cerebellar slices.

Abstract

SUMMARY1. Synaptic transmission from parallel fibres to Purkinje cells and its modification by paired stimulation of parallel fibres and climbing fibres were studied in in vitro slices of the cerebellum obtained from guinea-pigs.2. Intracellular recordings were made from Purkinje cells, mainly from dendrites in the middle third of the molecular layer, but also, in a few cases, from somata.Climbing fibres were activated by stimulation of the white matter, while parallel fibres were stimulated with an electrode placed near the pial surface of the molecular layer.3. Stimulation of the white matter elicited antidromic spikes, all-or-none climbing fibre responses, disynaptic responses through mossy fibres and parallel fibres, and trisynaptic responses through inhibitory interneurones. Climbing fibre responses were often followed by a small plateau potential, usually less than 2-3 mV in amplitude and less than 100 ms in duration, followed by a slow hyperpolarization which reached its peak in several seconds. Inhibitory inputs to Purkinje cells were blocked with picrotoxin for the experiments described below.4. Stimulation of the superficial molecular layer with currents less than 50 ,uA produced graded parallel fibre-mediated excitatory postsynaptic potentials (e.p.s.p.s) ranging from 4 to 8 mV in peak amplitude.5. Conjunctive stimulation of climbing fibres and parallel fibres at 4 Hz for 25 s induced depression of parallel fibre-mediated e.p.s.p.s in Purkinje cells, both in the peak amplitudes and in the slopes. The depression was about 30 % on average and lasted for more than 50 min.6. No such depression occurred when the intensity of the white matter stimulation was set just subthreshold for the climbing fibre innervating the Purkinje cell under study. Instead, the parallel fibre-mediated e.p.s.p.s were moderately potentiated for a period ranging from 10 to 50 min. Repetitive stimulation of the climbing fibre alone did not affect parallel fibre-mediated e.p.s.p.s.7. Immediately after the conjunctive stimulation or the repetitive stimulation of climbing fibres alone, a transient hyperpolarization which lasted for several minutes was seen. Its time course was similar to that of the hyperpolarization following a climbing fibre response. Except for this, there were no associated changes in the membrane potential, the input resistance, or the magnitudes of climbing fibre responses in any of the cases mentioned in 5 and 6 above.

A Mechanism for Savings in the Cerebellum

“…C limbing fiber inputs controlled activity-dependent plasticity at gr3Pk j synapses. L ong-term depression (LTD) was induced in gr3Pk j synapses that were active at the time of a climbing fiber input (Sakurai, 1987;Ito, 1989;Hirano, 1990;Linden, 1994), whereas long-term potentiation (LTP) was induced in gr3Pk j synapses that were active in the absence of a climbing fiber input (Sakurai, 1987;Hirano, 1990;Shibuki and Okada, 1992;Salin et al, 1996). The precise interval of time between granule cell and climbing fiber activation that is required for induction of LTD remains under investigation.…”

“…In addition, the simulation incorporated recent evidence for plasticity in both the cerebellar cortex ( gr3Pkj synapses) and cerebellar nucleus (mf3nuc synapses) (Robinson, 1976;Perrett et al, 1993;Raymond et al, 1996;Mauk, 1997). Based on empirical evidence, plasticity in the cerebellar cortex was controlled by climbing fiber inputs such that gr3Pkj synapses active during a climbing fiber input decreased in strength (LTD) and those active in the absence of a climbing fiber input increased in strength (LTP) (Sakurai, 1987;Ito, 1989;Hirano, 1990;Shibuki and Okada, 1992;Linden, 1994;Salin et al, 1996). As first suggested by Miles and Lisberger (1981) and supported more recently by theoretical and empirical (Perrett and Mauk, 1995;Aizenman and Linden, 2000) analyses, plasticity in the cerebellar nucleus was controlled by inhibitory inputs from Purkinje cells.…”

Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

“…Paired stimulation of parallel and climbing fibers induces LTD (Chen & Thompson, 1995;Schreurs, Oh, & Alkon, 1996;Freeman, Shi, & Schreurs, 1998), but parallel fiber stimulation without climbing fiber stimulation can induce LTP (Sakurai, 1987;Salin, Malenka, & Nicoll, 1996). It is possible that the parallel fiber-alone stimulation that presumably occurs during the non-reinforced compound stimulus in conditioned inhibition training induces LTP in Purkinje cells.…”

Active zones for presynaptic plasticity in the brain

“…Parallel fiber LTP occurs upon low-frequency stimulation in the absence of climbing fiber activation. [79][80][81][82][83][84][85] In a very similar manner as it happens at the hippocampal mossy fiber, parallel fiber LTP seems to be triggered by a presynaptic Ca 2 þ influx, and it is resistant to blockers of glutamate receptors and Ca 2 þ chelation at postsynaptic Purkinje cells. 81,[86][87][88] In addition, cerebellar granule cells in culture stimulated to release neurotransmitters were shown to activate glutamate-evoked inward currents in adjacent glial cells driven by AMPA/kainate receptors.…”