Pharmacological properties of inhibitions in the cerebellar cortex

Bisti, Silvia; Iosif, G.; Marchesi, G; Strata, Piergiorgio

doi:10.1007/bf00234908

Cited by 63 publications

(17 citation statements)

References 46 publications

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“…The currents that we attribute to synapses from basket cells are bicucullinesensitive, which establishes the involvement of GABAA receptors, and GABA is the probable transmitter at the basket cell-Purkinje cell synapse (10)(11)(12). These currents are quite variable in size, compatible with the idea that numerous basket cells synapse with a single Purkinje cell, but with different synaptic weights.…”

Section: Discussionsupporting

confidence: 53%

Synaptic currents in cerebellar Purkinje cells.

Konnerth

Llano

Armstrong³

1990

Proc. Natl. Acad. Sci. U.S.A.

363

273

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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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Section: Discussionsupporting

confidence: 53%

Synaptic currents in cerebellar Purkinje cells.

Konnerth

Llano

Armstrong³

1990

Proc. Natl. Acad. Sci. U.S.A.

363

273

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“…At least two convulsant substances, picrotoxin and bicuculline, have been claimed to be specific antagonists of GABA in a wide variety of neuronal structures. Iontophoretically applied picrotoxin seems to antagonize GABA actions on the crayfish neuromuscular junction (Takeuchi and Takeuchi, 1969) and on neurons in the oculomotor nucleus (Obata and Highstein, 1970), cuneate nucleus (Galindo, 1969), spinal cord (Engberg and Thaller, 1970), hypoglossus nucleus (ten Bruggencate and Sonnhof, 1972), Deiters' nucleus (ten Bruggencate and Engberg, 1971), olfactory bulb (Nicoll, 1971), cerebral cortex (Hill et at., 1972a), and cerebellar cortex (Woodward et at., 1971;Bisti et at., 1971). Similarly, bicuculline applied iontophoretically antagonizes GABA actions on the crayfish neuromuscular junction (Takeuchi and Onodera, 1972), and on neurons in Deiters' nucleus (Curtis et aI., 1970d), spinal cord (Curtis et at., 1970a, olfactory bulb (Nicoll, 1971), cuneate nucleus (Kelly and Renaud, 1971), cerebral and cerebellar cortex (Curtis and Felix, 1971 b;Curtis et at., 1970 b;Bisti et at., 1971), crayfish stretch receptor (McLennan, 1970), lateral vestibular nucleus and ventrobasal thalamic nucleus (Curtis et at., 1971b), and ventromedial hypothalamus (Dreifuss and Matthews, 1972).…”

Section: Effects Of Compounds On the Interaction Of Gaba With Its Posmentioning

confidence: 93%

Biochemical Pharmacology of GABA in CNS

Tapia

1975

Amino Acid Neurotransmitters

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“…In view of the proven function of GABA as the neurotransmitter of the basket synapses on the Purkinje cell soma (Eccles et al, 1967;Curtis et al, 1971;Woodward et al, 1971;Bisti et al, 1971), the major GABA-sensitive site located at the site of the Purkinje cell body (around 0 pm, Figure 2a) is considered to represent the GABA receptor sites on the basket B.J.P. 69/3E neuronal synapses on the Purkinje cell soma.…”

Section: \ I I Y 1antagonistic Actions Of Picrotoxin and Strychninementioning

confidence: 99%

“…Although it appears to be established that GABA is a neurotran,smitter of the inhibitory synapses of the cerebellar basket interneurones on the soma of the Purkinje cell (Curtis, Duggan, Felix, Johnston & McLennan, 1971;Woodward, Hoffer, Siggins & Oliver, 1971;Bisti, Josif, Marchesi & Strata, 1971), the transmitter of the stellate interneurones is yet to be identified. However, recent investigations by Nadi, McBride & Aprison (1977) and by Frederickson, Neuss, Morzorati & McBride (1978) suggest a possible transmitter role of taurine in the stellate neuronal synapses.…”

Section: Introductionmentioning

confidence: 99%

Localization of Sensitive Sites to Taurine, Γ‐aminobutyric Acid, Glycine and Β‐alanine in the Molecular Layer of Guinea‐pig Cerebellar Slices

Okamoto

Sakai

1980

British J Pharmacology

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1 The localization, in the molecular layer of guinea-pig cerebellar slices, of the sites most sensitive to iontophoretically applied taurine, y-aminobutyric acid (GABA), glycine and P-alanine was investigated. 2 The most sensitive sites were located (expressed as the distance from the Purkinje cell body to the pial surface): 0 rm, 60 pm and 220 pm for taurine; 0 ptm and 180 psm for GABA; 80 tm and 200 pm for glycine, and 80 pm, 180 pm and 300 j.m for /-alanine. 3 The sensitive site (at 0 pm) to GABA was considered to represent the basket synapses on the Purkinje cell soma, while the sites (60 to 80 pm and 200 to 300 pm) for taurine, glycine and /-alanine were tentatively assigned to the synapses of the stellate neurones on the Purkinje cell dendrites. 4 Inhibitory actions of all four amino acids tested at the most sensitive sites were antagonized by both picrotoxin and strychnine. 5 The possibility that taurine might be the neurotransmitter of the stellate neurones in guinea-pig cerebellum is discussed.

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Pharmacological properties of inhibitions in the cerebellar cortex

Cited by 63 publications

References 46 publications

Synaptic currents in cerebellar Purkinje cells.

Synaptic currents in cerebellar Purkinje cells.

Biochemical Pharmacology of GABA in CNS

Localization of Sensitive Sites to Taurine, Γ‐aminobutyric Acid, Glycine and Β‐alanine in the Molecular Layer of Guinea‐pig Cerebellar Slices

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