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Inhibitory events on cultured neurons
INTERNATIONAL
688
SYMPOSIUM
ON GABA
Al22
All9
INHIBITORY EVENTS ON CULTURED NEURONS J.L. Barker, J.F. MacOonald, R.N. McBurney and T.G. Smith, Jr. Laboratory of Neurophysiology, NINCOS, NIH, Bethesda, MD 20205. Spinal neurons were dissociated from mouse embryos and grown in tissue culture until they were large enough to apply conventional intracellular recording and voltage clamp techniques. Endogenous and exogenous ligands were applied to individual cells by iontophoresis or pressure. The neutral amino acids activated a Cl- ion conductance an all spinal cord neurons tested. Fluctuation analysis showed that specific amino acids activated single channels with distinctively different properties. Interactions betweenthe different amino acids suggested that they may share a common conductance mechanism. GABA-activated Cl- ion conductance and inhibitory synaptic currents could be modulated by a variety of convulsant and anticonvulsant drugs. The results suggest that 300 GABA-activated channels contribute to a single quanta1 synaptic event on cultured spinal newon~. That GABA may not always play an inhibitory role in the nervous system was revealed by the fact that nananolar concentrations lowered threshold for action potentialgeneration and enhanced repetitive firing in every cell tested, thus effectively increasing neuronal excitabilit The results -?.+ suggest that GABA alters neuronal excltabl ,ty lndlrectly through synaptic activation of Cl- ion conductance and directly through effects on the membrane mechanisms underlying spike generation.
.
Al23 A120 OIIATE EFFECTS ON MOTILITY:POSSIBLE ROLE OF INTEHACTIONS BETWEEN GABA-ERGIC AND DOPAMINERGIC NEURONS. Kuschinsky,K.,Genc.E.,Havemann,U.,and Winkler,M., Max Planck Institute for Experimental Medicine, 3400 Gtittlngen,Fed. Rep. of Germany The role of the caudate nucleus in mediating opiaid-induced rigidity was evaluated in rats by measuring the electromyographical (EMG) activity in the gastrocnemius-soleus muscle. A naloxone-reversible EMG activation could be induced not only by systemic administration of morphine, but 9ls.o by local administration of morphine or D-ala -metenkephalinamide into the head of the caudate nucleus. Bilateral cbcxoiesions of the caudate nucleus with kainic acia abolished the EMG activation induced by systemic administration of morphine. Lesions of this kind did not abolish the increase of striate1 DOPAC after systemic administration of mornhine: in fact. the lesions even enhanced it.
A
synopsis
of
our
results
and
those
of
other
authors suggests that opiates induce rigidity by direct actions on neurons, the cell bodies of which are located in the caudate nucleus - probably on GABAergic neurons. The increase of dopamine turnover, on the other hand, is mediated via different neurons.
A121
A124
688
SYMPOSIUM
ON GABA
Al22
All9
INHIBITORY EVENTS ON CULTURED NEURONS J.L. Barker, J.F. MacOonald, R.N. McBurney and T.G. Smith, Jr. Laboratory of Neurophysiology, NINCOS, NIH, Bethesda, MD 20205. Spinal neurons were dissociated from mouse embryos and grown in tissue culture until they were large enough to apply conventional intracellular recording and voltage clamp techniques. Endogenous and exogenous ligands were applied to individual cells by iontophoresis or pressure. The neutral amino acids activated a Cl- ion conductance an all spinal cord neurons tested. Fluctuation analysis showed that specific amino acids activated single channels with distinctively different properties. Interactions betweenthe different amino acids suggested that they may share a common conductance mechanism. GABA-activated Cl- ion conductance and inhibitory synaptic currents could be modulated by a variety of convulsant and anticonvulsant drugs. The results suggest that 300 GABA-activated channels contribute to a single quanta1 synaptic event on cultured spinal newon~. That GABA may not always play an inhibitory role in the nervous system was revealed by the fact that nananolar concentrations lowered threshold for action potentialgeneration and enhanced repetitive firing in every cell tested, thus effectively increasing neuronal excitabilit The results -?.+ suggest that GABA alters neuronal excltabl ,ty lndlrectly through synaptic activation of Cl- ion conductance and directly through effects on the membrane mechanisms underlying spike generation.
.
Al23 A120 OIIATE EFFECTS ON MOTILITY:POSSIBLE ROLE OF INTEHACTIONS BETWEEN GABA-ERGIC AND DOPAMINERGIC NEURONS. Kuschinsky,K.,Genc.E.,Havemann,U.,and Winkler,M., Max Planck Institute for Experimental Medicine, 3400 Gtittlngen,Fed. Rep. of Germany The role of the caudate nucleus in mediating opiaid-induced rigidity was evaluated in rats by measuring the electromyographical (EMG) activity in the gastrocnemius-soleus muscle. A naloxone-reversible EMG activation could be induced not only by systemic administration of morphine, but 9ls.o by local administration of morphine or D-ala -metenkephalinamide into the head of the caudate nucleus. Bilateral cbcxoiesions of the caudate nucleus with kainic acia abolished the EMG activation induced by systemic administration of morphine. Lesions of this kind did not abolish the increase of striate1 DOPAC after systemic administration of mornhine: in fact. the lesions even enhanced it.
A
synopsis
of
our
results
and
those
of
other
authors suggests that opiates induce rigidity by direct actions on neurons, the cell bodies of which are located in the caudate nucleus - probably on GABAergic neurons. The increase of dopamine turnover, on the other hand, is mediated via different neurons.
A121
A124