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G V Goddard

Publications and source records attributed to G V Goddard.

41 records · Page 3Linked to original sources
PubMedDate not supplied

Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression.

All synaptically-based neuropsychological theories of learning postulate that there are changes resulting from neural activity which are long-lasting and confined to specific sets of synapses. In the past decade a form of synaptic strengthening known as long-term potentiation (LTP) has been found which results from high-frequency neural activity and is of sufficient duration to model as a learning mechanism. Some early tests of the synaptic specificity of LTP in area CA1 of the hippocampus indicated that although LTP was specific to the tetanized pathway, in a converging untetanized pathway it was associated with depression of synaptic transmission lasting for at least 30 min. However, others have found that this heterosynaptic depression more usually decays within 5-15 min post-tetanus despite the maintenance of LTP in the tetanized pathway. Similarly, in the dentate gyrus (DG), LTP of either the lateral (LPP) or medial (MPP) components of the perforant path afferents has been associated with only short-lasting reciprocal heterosynaptic depression. Here, using more detailed measurement of stimulus intensity curves, we report that tetanization of either MPP or LPP reliably depresses synaptic transmission in the other pathway for at least 3 h. This heterosynaptic depression, considerably smaller than the usual magnitude of LTP, was obtained regardless of whether LTP had been produced in the tetanized homosynaptic pathway. Heterosynaptic long-term depression was not observed if the test pathway had been previously tetanized.

Animals↗
PubMedDate not supplied

Is adenosine an endogenous anticonvulsant?

The anticonvulsant properties of adenosine were tested pharmacologically on amygdala-kindled seizure activity in rats. The adenosine analogue 2-chloroadenosine and the adenosine uptake blocker papaverine both increased the latency to behavioral clonus as well as reduced the duration and severity of the clonic motor convulsion. Both drugs, however, failed to alter the postkindling afterdischarge (AD) threshold. Theophylline, an adenosine antagonist, had the opposite effects, prolonging the AD and motor seizure durations and facilitating partially kindled seizures, but again not altering the prekindling or postkindling AD thresholds of amygdala-elicited seizures. In contrast, carbamazepine raised AD thresholds, suggesting that it does not produce its anticonvulsant effects through adenosine systems. Since endogenous adenosine can impede seizure spread and seizure continuation, but does not affect seizure initiation from the amygdala, perhaps endogenous adenosine has the special property of being brought into play as an anticonvulsant only by the seizure itself.

2-Chloroadenosine↗
PubMedDate not supplied

The substantia nigra is an important site for the containment of seizure generalization in the kindling model of epilepsy.

To investigate the role of the substantia nigra (SN) in kindling, electrical stimulation of the SN was delivered at various times before or after stimulation of the amygdala (AM) or pyriform cortex during or after kindling in rats. The results were as follows: Ipsilateral SN stimulation delivered prior to each AM kindling stimulation for 14 days significantly retarded the appearance of Stage 4 and 5 seizures and shortened the afterdischarge (AD) duration. Bilateral SN prestimulation blocked seizure generalization in some AM- or pyriform cortex-kindled animals, prolonged the latency to bilateral forelimb clonus in others, and shortened the AD duration of the kindled seizure in a current intensity-dependent fashion. These effects were only partially antagonized by haloperidol, but were completely abolished by picrotoxin. The picrotoxin alone significantly reduced the latency. Almost no effect was found when the SN stimulation was delivered after the onset of bilateral forelimb clonus. We conclude that the SN might be an important mediator of the early aspects of seizure generalization from limbic epileptic foci. The relative involvements of GABAergic gamma-aminobutyric acid and dopaminergic systems of the SN in this inhibitory function are discussed.

Amygdala↗