Epileptic activity as a tool in neurobiology.
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Biomedical subjects
Publications and source records attributed to U Altrup.
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1. Effects of the hypnotic drug etomidate were studied with intracellular recordings of the identified neurons B1 to B4 of the buccal ganglia of Helix pomatia. 2. At threshold doses of 10 mumol/l, etomidate mainly affected interneuronal networks. 3. In concentrations above 200 mumol/l, the drug induced typical epileptic activities (paroxysmal depolarization shifts, PDS). Neurons B1 to B4 generated epileptic activities in differential concentration ranges. PDS were synchronized via electrical contacts. PDS could be blocked by the "calcium antagonist" verapamil but not by a block of chemical synaptic transmission. 4. In comparison with the epileptogenic drug pentylenetrazol, effective doses of etomidate to induce PDS were about 100 times lower.
Changes of free calcium concentration at the outer neuronal surface during paroxysmal depolarization shifts elicited by pentylenetetrazol were measured. Investigations were performed on the identified neuron B3 of the buccal ganglion of Helix pomatia. Extracellular calcium concentration was recorded by calcium-selective microelectrodes. The extracellular calcium concentration steeply decreased with the commencement of paroxysmal depolarization and started to reincrease when the paroxysmal depolarization had reached its plateau level. It is concluded that an influx of calcium ions takes place during paroxysmal depolarization shifts.
The effect of the epileptogenic drug pentylenetetrazol (PTZ) on the shape of dendrites of identified snail neurons was investigated. Comparison between control and test preparations revealed that changes in the shape of dendrites appeared after PTZ treatment: (i) the number of dendrites, especially filopodia-like structures, increased; (ii) separations and involutions of dendrites occurred. Both of these changes of dendrites were found either separately or in combination.
The identified giant neurons B1 and B2 in the buccal ganglia of Helix pomatia were studied with electrophysiological and morphological techniques in order to establish a baseline for the study of neuronal communication in a relatively simple nervous system. Different synaptic inputs to neurons B1 and B2 were found to come from neurons of the buccal ganglia and to come via buccal nerves. In the epithelium of the pharynx, fibers of bipolar peripheral neurons could be stained, the central fibers of which probably contribute to the synaptic inputs of neurons B1 and B2. The dendrites of neurons B1 and B2 are mainly situated in anterior and lateral parts of the neuropil of the buccal ganglia, respectively. The axon of neuron B1 was traced to the esophagus/stomach. Intracellular stimulation of the neuron induces both a contraction of the longitudinally oriented fibers and an increase in the amplitude of spontaneously occurring peristaltic contractions of the esophagus. The axons of neuron B2 run to both salivary glands. Thin axon collaterals showing multiple swellings follow the bases of the epithelial cells of the salivary gland. The functioning of neurons B1 and B2, which are homologous to giant neurons in the buccal ganglia of other molluscs, is discussed.
In identified neurons of Helix pomatia nerve stimulation evoked depolarizations of short latencies. The mechanisms underlying these potentials were studied by conventional electrophysiological and intracellular staining techniques. Most of the depolarizations behaved like chemically mediated postsynaptic potentials. The remaining responses can be regarded either as antidromic axonal action potentials (APs) or as electrotonic junction potentials. The differentiation between the latter alternatives and hence the identification of the axonal pathways of the impaled neurons proved to be difficult using conventional methods.
The axonal pathways and the synaptic inputs of the identified neurons B1 through B3 in the buccal ganglia of Helix pomatia were studied. The axons of neurons B1, B2 and B3 were found to run invariably within the ipsilateral posterior oesophageal nerve, ipsi- and contralateral salivary gland nerves, and ipsilateral cerebrobuccal connective, respectively. Synaptic responses could be elicited by stimulation of most of the nerves of the buccal ganglia. These consisted of an early depolarization which was most frequently followed by a longlasting de- or hyperpolarization. The shape of the synaptic response proved to be related to the different neurons.
Cellular actions of valproate (VPA) were studied using intracellular recordings of identified neuronal individuals in the buccal ganglia of Helix pomatia. Under nonepileptic conditions, VPA induced (a) a hyperpolarization, (b) slight changes in action potentials (AP), and (c) an increase in membrane resistance. Under epileptic conditions (i.e., during application of an epileptogenic drug), extracellular application of VPA decreased frequency of occurrence of epileptic depolarizations (early effect) and led to a decay in paroxysmal depolarizations (late effect). Intracellular injection of VPA could block epileptic activity in the treated neuron immediately. A metabolite of VPA (trans-2-en VPA) mainly lacked the late effect (decay in epileptic depolarizations) obtained with VPA. Results suggest that the early antiepileptic effect is exerted from the extracellular side of the neuronal membrane and that the late effect results from intracellular actions of VPA being delayed by slow access to an intracellular site.
High concentrations of valproate (VPA; greater than 20 mM) depolarized identified neuronal individuals in the buccal ganglia of Helix pomatia and transiently induced paroxysmal depolarization shifts (PDS). Threshold concentration of VPA for the induction of PDS was decreased (a) by increased seizure susceptibility, (b) by increased concentrations of derivatives of VPA, and (c) by increased H+ concentrations. Intrasomatic injection of VPA did not induce PDS. The epileptogenic action of VPA is believed to be exerted from the extracellular side of the cell membrane.
The buccal ganglia of Helix pomatia are used as model nervous structures in neurophysiological and in epileptological studies. Many basic problems concerning membrane physics, functioning of the single neurons and of neuronal networks can be studied easily using these ganglia. The model character mainly comes from the relative simplicity of this nervous system and that it contains large visually identifiable neurons. As in other invertebrate nervous systems, the large neurons have proved to be individuals showing the same functional and structural properties from one animal to the next.