Zinc induces hyperexcitability in the hippocampus.

The effects of zinc on neuronal excitability in rodent hippocampal slices were examined. In a paired-pulse protocol, the second population spike increased appreciably in the presence of zinc, whereas the first spike and the size of both population excitatory post-synaptic potentials remained unaffected. Changes in the second population spike produced by zinc were most pronounced when the afferents were stimulated with paired-pulses separated by 8-40 ms. The magnitude of altered excitability increased with the concentration of zinc in the perfusate. A long exposure to zinc in physiological concentration caused an epileptiform discharge followed by a period of depression. The effects of zinc could be mimicked with 1-3 microM bicuculline. We conclude that the integrity of the hippocampal inhibitory system is particularly vulnerable to zinc.

The Maturation of the Superior Collicular Map of Auditory Space in the Guinea Pig is Disrupted by Developmental Auditory Deprivation.

Guinea pigs, reared from birth in an environment of omnidirectional white noise, fail to develop a map of auditory space in the deeper layers of the superior colliculus. Collicular responses from such noise-reared animals reveal large auditory spatial receptive fields. The representation of auditory space in the colliculus shows no topographic order. Exposing developing animals to the noise environment only for restricted time periods showed that animals reared normally up to 26 days after birth (DAB) and then placed in the noise chamber could not construct spatial maps, whereas animals reared normally to 30 DAB and then placed in the noise chamber until the terminal mapping experiment could construct topographically organized spatial maps with local receptive fields. Limiting the noise exposure to the period between 26 and 30 DAB was sufficient to prevent spatial map formation. The failure to form a map of auditory space did not reflect environmental damage to the cochlea or the functional organization of the primary auditory pathway. The response thresholds of cochlear microphonics and of auditory responses in both the inferior and superior colliculus were normal in noise-reared animals. Similarly normal were the tonotopic organization and frequency tuning characteristics of inferior collicular neurons. The rearing environment thus appears to exert a selective effect upon the maturation of the superior collicular map of auditory space. We attribute this effect to the masking, by the omnidirectional broad-band noise, of discrete localized auditory stimuli. Cues deriving from these latter stimuli would appear to be necessary for the elaboration of the map of auditory space. This auditory experience operates during a 4 day crucial developmental period from 26 to 30 DAB. This is the same developmental time window as that during which visual experience is required for the construction of the map.

Effect of glutamate, aspartate and related derivatives on cerebellar purkinje cell dendrites in the rat: an in vitro study.

1. The responses of Purkinje cells to short duration (pulse) ionophoretic applications of L-aspartate (L-asp), L-glutamate (L-glu), N-methyl DL-aspartate (NMDLA) and quisqualic acid in their dendritic fields were studied in vitro on sagittal slices of lobules IX and X of the adult rat cerebellum.2. Pulse application of L-asp or L-glu evoked transient and dose-dependent increases in the firing rate of the simple spikes recorded extracellularly as single units. When the ionophoretic electrode was positioned in the dendritic field of the Purkinje cells, the lowest thresholds for L-glu and L-asp mediated excitations of the cells were as low as 25 and 35 pC respectively, with a latency for maximal responses as brief as 7 ms.3. In intracellular recordings these excitatory responses consisted of depolarizations of up to 18 mV in amplitude and with depolarizing slopes up to 0.52 mV/ms. They were generally unaccompanied by changes in cell input resistance in contrast to the marked decrease which occurred in response to steady applications of large doses of L-asp and L-glu.4. The spatial distribution of the excitatory sites confirmed that the dendritic sensitivity to L-glu was greater than that of the soma and showed that the same was true for L-asp. In 34% of cells the sensitivity for L-asp declined markedly in the upper region of the molecular layer, whereas it remained high for L-glu; no such differential sensitivity was detected in the remaining 66% of cells.5. Inhibitory responses, antagonized by 10(-5) M-bicuculline in the bath, were also induced in Purkinje cells by L-glu and L-asp when the ionophoretic electrode was withdrawn from the excitatory sites by as little as 8 mum and up to 40 mum upward or downward along the track of parallel fibres or positioned as far as 250 mum laterally.6. Whenever it was applied in the molecular layer, the pulse application of NMDLA elicited no excitatory response in Purkinje cells recorded extra or intracellularly. However, slow depolarizations accompanied by a slight increase in cell input resistance were obtained with steady applications of 20-50 nA of the drug for 20-30 s.7. In contrast, pulse application of quisqualic acid appeared to have the same type of fast excitatory effect on Purkinje cells as L-asp and L-glu, but its potency was greater and its action more prolonged. Furthermore, its steady application led to an abrupt and marked decrease in cell membrane resistance.8. The excitatory effects of L-asp, L-glu and quisqualic acid were antagonized by L-glutamic acid diethyl ester more consistently than by D-alpha-aminoadipate, suggesting together with previous observations that L-asp and L-glu act on Purkinje cells via quisqualic acid rather than via NMDLA receptors.

Morphological and electrophysiological characteristics of rat cerebellar slices maintained in vitro.

1. The morphological and electrophysiological characteristics of sagittal cerebellar slices of adult rat cerebellum maintained in vitro were studied. 2. The ultrastructural preservation of the different neuronal cell types in many areas of these slices after 2-3 h incubation was very similar to that observed in material fixed in situ. A limited degree of glial swelling was observed in some regions. 3. The conduction velocity of parallel fibres was within the normal in vivo range and the fibres retained their ability to activate Purkinje cells and inhibitory interneurones. 4. Purkinje cells, recorded intrasomatically, responded to white matter stimulation with characteristic antidromic activation and climbing fibre responses, and typical parallel fibre responses were evoked following parallel fibre stimulation. 5. Climbing fibre excitatory post-synaptic potentials (e.p.s.p.s) were very similar whether recorded in the dendrites or somata of Purkinje cells. By contrast, marked differences in the associated spike potentials were evident, the initial fast, low-threshold somatic spike appearing in the dendrites as a slow, high-threshold spike. The secondary spikes, both in the soma and dendrites, were of the latter type. 6. The initial somatic spike was readily inactivated by cell depolarization but resisted moderate hyperpolarization, whereas the converse was true for the slow, high-threshold spikes recorded in the dendrites. These differences suggest that these responses are generated in the soma and in the dendrites respectively. 7. Climbing fibre and parallel fibre e.p.s.p.s recorded in Purkinje cell somata were reversed under depolarizing current injected through the recording micro-electrode. As in vivo, the parallel fibre e.p.s.p.s was more sensitive to injected current than the climbing fibre e.p.s.p. in several instances, despite the more proximal location of the synapses involved.