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G L Collingridge

Publications and source records attributed to G L Collingridge.

At least 145 records · Page 8Linked to original sources
PubMed1984

Inhibitory post-synaptic currents in rat hippocampal CA1 neurones.

Spontaneous synaptic currents were recorded in voltage-clamped CA1 neurones in rat hippocampal slices at room temperature (21-25 degrees C). The currents, which could be seen at the resting membrane potential only when cells were loaded with chloride ions, were blocked by bicuculline. It was concluded that they were inhibitory post-synaptic currents (i.p.s.c.s) generated by the opening of chloride-selective channels activated by gamma-aminobutyric acid (GABA). In twenty-nine cells, ten to forty-five i.p.s.c.s were recorded at a potential between -75 and -85 mV. In every cell, i.p.s.c.s varied widely in amplitude with an average coefficient of variation of 28.7%. The mean amplitude varied from 0.22 to 1.16 nA with an average of 0.52 nA. Reversed (outward) currents could be recorded from cells voltage clamped at positive potentials. Null potentials varied between -20 and +20 mV, the variability being attributed to differences in chloride loading. Most currents had a rapid growth phase with a mean growth time (20-80% of peak) of 1.1 ms followed by a slower decay phase. The decay phase was exponential with a single time constant. The average decay time constant (tau D) ranged from 8.3 to 16.2 ms with a mean value of 11.0 ms. The rate of decay of currents was affected by membrane potential. tau D decreased exponentially with hyperpolarization in the range from +40 to -120 mV with an average volt constant (H value) of 146 +/- 9.6 mV (mean +/- 1 S.E. of mean, n = 17). The mean value of tau D at 0 mV was 19 ms. In some cells, growth times also decreased with hyperpolarization. The decay of currents was faster at higher temperatures but remained exponential. At 32 degrees C, the average tau D at 0 mV was 8.3 ms (n = 5) giving a Q10 value of 3.3 for the decay time constant at 0 mV. The frequency and mean amplitude of i.p.s.c.s were reduced by tetrodotoxin (TTX) or cadmium, indicating that many of the currents were generated by action potentials in presynaptic terminals. The spontaneous 'miniatures' remaining had the same time course and voltage sensitivity as currents recorded in normal solutions. Pentobarbitone (50-100 microM) greatly prolonged the decay of i.p.s.c.s but had no discernible effect on their amplitude or growth phase.

Action Potentials↗
PubMed1984

The action of some analogues of the excitatory amino acids in the dentate gyrus of the rat.

We have confirmed that gamma-D-glutamylglycine and the L-isomer of 2-amino-4-phosphonobutyric acid, and have shown also that L-2-amino-5-phosphonovaleric (L-APV) acid, are antagonists of synaptic excitations of dentate granule cells induced from both lateral and medial perforant paths. The N-methyl-D-aspartic acid (NMDA) antagonist D-APV is without effect. The synaptic antagonists reduce the presynaptic fibre volley particularly in the lateral path, suggesting that a reduced transmitter output contributes to their action. NMDA receptors exist upon the granule cells, but they are not involved with these synaptic process.

2-Amino-5-phosphonovalerate↗
PubMed1983

Effects of kainic and other amino acids on synaptic excitation in rat hippocampal slices: 1. Extracellular analysis.

The actions of kainic acid on excitatory synaptic responses in rat hippocampal slices have been investigated and compared with the effects of other excitatory amino acids. Kainate administered iontophoretically or via the superfusate produced a large and long lasting potentiation of the population spike evoked in the CA1 region by Schaffer collateral-commissural stimulation. This potentiation was associated with a reduction in the field EPSP recorded in the dendritic region (stratum radiatum) but with no change in the presynaptic fibre volley or with any long lasting alteration in the antidromic population spike. The results suggest that one effect of kainate may be to produce dendritic depolarisation in CA1 pyramidal neurones. Kainate in equivalent amounts elicited similar potentiations of the population spike recorded in the dentate gyrus in response to either lateral or medial perforant path stimulation. Smaller amounts of kainate than those required to affect either CA1 or dentate pathways were able to potentiate the mossy fibre-evoked population spike in the CA3 region. Folic acid, which shares kainate's ability to produce seizures and distant brain damage when injected into the brain, elicited similar potentiations of synaptic excitation. Higher doses of folate than of kainate were required which is consistent with its weaker epileptogenic actions in vivo. In contrast, N-methyl-aspartate, ibotenate, L-glutamate and L-aspartate were unable to mimic kainate's potentiating action. In higher doses the substances depressed the population spike for long periods. These data suggest that potentiation of synaptic events may underlie the ability of kainate (and folate) to elicit seizures and distant brain damage.

Amino Acids↗
PubMed1983

The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro.

1. The effects of the ionophoretic application of a number of excitatory amino acids and antagonists to the dendrites of CA1 neurones of rat hippocampal slices maintained in vitro were examined. Cells were excited by N-methyl-DL-aspartate (NMA), kainate, quisqualate, L-aspartate and L-glutamate; NMA was unique in causing cells to fire in bursts of repetitive discharges in contrast to the sustained firing seen with the other compounds. 2. D-(-)-alpha-aminoadipate (DAA) and (+/-)-2-amino-5-phosphonovalerate (APV) were selective NMA antagonists, the latter appearing to be the more potent; in addition both compounds potentiated the responses to kainate and quisqualate. L-glutamate excitations were affected less by APV than were those of L-aspartate. The antagonist properties of APV appeared to reside with the D-(-)-isomer. 3. gamma-D-glutamylglycine (DGG) in low ionophoretic doses inhibited NMA-, kainate- and aspartate-induced cell firing but at higher doses the quisqualate and glutamate responses were also decreased. 4. Kainate and NMA responses were blocked by D-(-)-2-amino-4-phosphonobutyrate (D-APB) which also had some action against the excitatory effects of L-aspartate. L-APB had no antagonistic effects, but often produced potentiation of amino acid excitations or was itself an excitant. 5. The effects of NMA and those of kainate and quisqualate were blocked by (+/-)-cis-2,3-piperidine dicarboxylate (PDA), but this compound itself had a direct excitatory effect. L-glutamate diethylester (GDEE) did not show specific antagonism of any amino acid excitations. 6. DGG and APV did not affect ACh excitations and these selective antagonists should be of value in studying the involvement of the excitatory amino acids in synaptic transmission in the hippocampus. Because they are less potent and/or have complicating direct effects PDA, GDEE, D- and L-APB may be less useful in this regard.

2-Amino-5-phosphonovalerate↗
PubMed1983

Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus.

1. The effects of excitatory amino acids and some antagonists applied by ionophoresis to stratum radiatum in the CA1 region of rat hippocampal slices were examined on the locally recorded field e.p.s.p. evoked by stimulation of the Schaffer collateral-commissural projection. 2. L-glutamate, L-aspartate and the more potent and selective excitatory amino acids quisqualate, kainate and N-methyl-DL-aspartate (NMA) depressed the e.p.s.p., presumably through depolarization and/or a change in membrane conductance. 3. The depression induced by kainate considerably outlasted the period of ejection whereas NMA depressions were rapidly reversible and were often followed by a potentiation of the e.p.s.p. In higher doses NMA also depressed the presynaptic fibre volley. The possible involvement of these effects in neurotoxicity and synaptic plasticity is raised. 4. The selective NMA antagonist, DL-2-amino-5-phosphonovalerate (APV) applied in doses which abolished responses to NMA, had no effect on the e.p.s.p. but prevented long term potentiation (l.t.p.) of synaptic transmission evoked by high frequency stimulation of the Schaffer collateral-commissural pathway. Other antagonists which had little or no effect on normal synaptic transmission included D-alpha-aminoadipate (DAA), the optical isomers of 2-amino-4-phosphonobutyrate (APB) and L-glutamate diethylester (GDEE). 5. In contrast, gamma-D-glutamylglycine (DGG), applied in amounts which affected quisqualate and kainate actions as well as those of NMA, was an effective synaptic antagonist whilst having no effect on the presynaptic fibre volley. 6. These results indicate that the synaptic receptor in the Schaffer collateral-commissural pathway may be of the kainate or quisqualate type. Although NMA receptors do not appear to be involved in normal synaptic transmission in this pathway they may play a role in synaptic plasticity. The interaction of L-glutamate and L-aspartate with these receptors is discussed.

Action Potentials↗
PubMed1982

Actions of substance P and opiates in the rat substantia nigra.

The actions of iontophoretically applied substance P, morphine and met-enkephalin on single neurones in the substantia nigra and overlying reticular formation were investigated. None of these agents affected nigrostriatal compacta neurones, however, reticulata and reticular formation neurones were often excited by morphine and substance P, and the latter inhibited by met-enkephalin. These results suggest that activation of the dopaminergic nigrostriatal pathway by these substances may be mediated indirectly, possibly via reticulata or reticular formation neurones.

Animals↗
PubMed1982

The in vitro inhibition of GABA release by tetanus toxin.

The in vitro effects of tetanus toxin on the potassium (K+)-evoked release of radiolabelled gamma-aminobutyric acid (GABA) from slices prepared from substantia nigra of the rat have been investigated. The addition of tetanus toxin (750-15,000 mouse LD50 ml-1) to the slices produced a dose- and time-dependent reduction in the K+-evoked release of [3H]GABA. These effects of the toxin were diminished at low temperature and in the absence of calcium ions in the bathing medium. It is suggested that this relatively simple in vitro system may allow more quantitative studies to be made concerning the action of the toxin on inhibitory amino acid release from the mammalian central nervous system.

Animals↗
PubMed1982

Evidence for the participation of nigrotectal gamma-aminobutyrate-containing neurones in striatal and nigral-derived circling in the rat.

The gamma-aminobutyrate-containing nature of nigrotectal neurones and the possible involvement of the tectum in circling behaviour were investigated in the rat. Electrolytic or kainic acid lesions of the substantia nigra reduced gamma-aminobutyrate levels on average by 19-29% in intermediate and deep, but not superficial superior colliculus. Placement of lesions or injection of muscimol (40 ng) into these gamma-aminobutyrate-innervated layers of superior colliculus gave only weak ipsilateral posturing or circling that was intensified by apomorphine, but which strongly antagonized contraversive apomorphine-induced circling in 6-hydroxydopamine pretreated rats(lateral greater than medial sites). Contraversive circling to unilateral muscimol (40 ng) was significantly attenuated by lesions or muscimol injections placed in the ipsi- or contralateral superior colliculus. Picrotoxin (40 ng) and tetanus toxin (30 mouse LD50 doses) evoked explosive motor behaviour from medial colliculus and vigorous contraversive circling when injected into the lateral colliculus. The latter offset ipsiversive asymmetries to kainate (0,8 micrograms) in the corresponding substantia nigra. Bilateral intratectal picrotoxin produced hyperactivity that reversed haloperidol catalepsy. Similar bilateral administration of muscimol did not produce catalepsy but a state of frozen immobility. Kainic acid introduced into the superior colliculus gave mixed excitatory-inhibitory responses initially followed by ipsiversive circling only and loss of tectal perikarya. None of these drug effects occurred from the overlying cerebral cortex or subjacent tegmentum. We propose that separate medial "non-postural" and lateral "postural" tectal locomotor regions may exist in the superior colliculus that are situated within a striato-nigrotectal outflow system capable of influencing the animal's motor activity and posture.

Animals↗
PubMed1982

Reversible effects of tetanus toxin on striatal-evoked responses and [3H]-gamma-aminobutyric acid release in the rat substantia nigra.

1 The effects of sublethal doses of tetanus toxin on gamma-aminobutyric acid (GABA)-mediated synaptic transmission and [3H]-GABA release were studied in the rat substantia nigra. 2 Intranigral injections of tetanus toxin at 1-5 times the mouse LD50 dose produced ipsiversive circling behaviour which was maximal after 1 week and lasted 2-3 weeks. Rats then displayed normal behavior suggesting that the effects of the toxin were fully reversible. 3 In the treated nigra of circling rats there was a reduction in the striatal-evoked inhibition of compacta and reticulata neurones, but no change in their spontaneous firing rates. Some forms of striatal-evoked excitation were also reduced. Once rats had recovered from circling no alterations in the synaptic responses were detected. 4 In circling rats there were no differences in the sensitivities of neurones in the treated and untreated nigra to GABA or to other inhibitory neurotransmitters. 5 The Ca2+-dependent, K+-evoked release of [3H]-GABA from slices prepared from the treated nigra of circling rats was less than that from the untreated nigra of circling rats. No differences in nigral [3H]-GABA release were observed once rats had recovered from the circling behaviour. 6 The results demonstrate that doses of tetanus toxin which produce reversible behavioural effects can interfere reversibly with GABA-mediated synaptic transmission by a presynaptic mechanism which probably involves a reduction in transmitter release.

Animals↗
PubMed1981

The influence of striatal stimulation and putative neurotransmitters on identified neurones in the rat substantia nigra.

The response of two populations of neurones in the substantia nigra (nigro-striatal compacta neurones and reticulata neurones) to microelectrophoretically administered putative neurotransmitters and stimulation of the ipsilateral striatum has been investigated in anaesthetized rats. There were marked differences between compacta and reticulata neurones in respect to their action potential configurations, spontaneous firing rates and their responses to striatal stimulation. However, both compacta and reticulata neurones were excited and/or inhibited by striatal stimulation, although inhibition was usually the predominant response in both neuronal populations. Compacta neurones were strongly inhibited by noradrenaline (NA) and dopamine (DA) but were unaffected by acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). Reticulata neurones were excited by ACh and showed mixed responses to 5-HT, DA and NA. Excitant amino acids overdepolarized compacta neurones preventing them from firing rapidly, but induced large increases in reticulata neurone firing rate; effects that were readily antagonized by D-alpha-aminoadipate. Compacta neurones were less sensitive than reticulata neurones to GABA and glycine. The action of these inhibitory amino acids were selectively and reversibly antagonized by bicuculline methochloride and strychnine, respectively. The striatal-evoked inhibition of both compacta and reticulata neurones was reversibly reduced by bicuculline methochloride and irreversibly reduced by tetanus toxin, but was unaffected by strychnine. These results demonstrate that nigrostriatal-compacta neurones and reticulata neurones are physiologically and pharmacologically distinct neuronal populations and both receive inhibitory GABAergic and excitatory striatal inputs.

Animals↗
PubMed1980

Antidromic latency variations of nigral compacta neurones.

Variations in the antidromic latency of substantia nigra compacta neurones were commonly observed following striatal stimulation. These results provide electrophysiological evidence for a branched unmyelinated nigrostriatal pathway and demonstrate that the antidromic criterion of constant latency is not valid for this type of pathway.

Animals↗