Pharmacology of the dendritic action of acetylcholine and further observations on the somatic disinhibition in the rat hippocampus in situ.
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Biomedical subjects
Publications and source records attributed to E Cherubini.
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Considering that a well-defined dopaminergic projection from the mesencephalic structures to the rat frontal cortex has been demonstrated, the purpose of this research was to study the action of iontophoretically applied dopamine (DA) on intracellularly recorded rat frontal neurons. The stimulation of the substantia nigra (SN) and the ventral tegmental area (VTA) evoked EPSP-IPSP sequences in these cells. About 50% of the tested neurons, widely distributed in all the frontal cortex, responded to DA application and no difference in the response to DA was observed between neurons with monosynaptic inputs and neurons with polysynaptic inputs. The catecholamine depolarized the cell membrane and decreased the firing rate, generally without significant changes in membrane resistance, as already observed in rat and cat striatal cells. In some neurons the decrease of the spikes preceded the membrane depolarization. Considering the complex effect of DA on the electrical properties of these neurons, these results seem to be indicative of a mechanism of action dependent on metabolic changes.
In rats under urethane anesthesia, a twin set of multibarreled micropipettes was used to record simultaneously in situ the somatic population spike, the positive field and the dendritic negative field (EPSP) evoked by commissural stimulation, and to apply microiontophoretically GABAergic and cholinergic agents at each level. Relying on the typical somatic responses evoked by local application of GABA and acetylcholine (ACh), an electrode can be positioned in the pyramidal layer with good accuracy (in the range of 50 microns) and the pharmacology of the excitatory drive impinging upon the apical dendrite concomitantly investigated.
In the present study we analyze whether glycine satisfies some electrophysiological and biochemical criteria to consider it as a putative transmitter in the rat cerebral cortex. Intracellular recordings from rat sensory-motor cortex showed that in 15-20% of the tested neurons glycine hyperpolarized the cell membrane, decreased the firing rate and flattened the evoked EPSP-IPSP sequence by increasing the membrane conductance. The iontophoretic application of strychnine antagonized the block of 'spontaneous' firing and the membrane hyperpolarization induced by glycine. Moreover, in a group of neurons, strychnine decreased the amplitude and duration of the IPSP and brought back the membrane potential to resting values. Previously accumulated [3H]glycine and endogenous glycine were released from cortical synaptosomal preparations by depolarizing stimuli in a Ca2+-dependent way. The release pattern of glycine was qualitatively similar in cortical and in spinal synaptosomes. [14C]Glycine was rapidly synthetized from [14C]serine in cortical synaptosomal preparations, and the newly formed [14C]glycine was released by depolarizing stimuli in a Ca2+-dependent way. It is concluded that glycine, which is generally considered as an inhibitory neurotransmitter in the spinal cord, medulla and pons, may also have a transmitter role in a discrete number of cortical neurons of some mammalian species.U
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In rats under urethane anaesthesia, microiontophoretic application of muscarinic or nicotinic agents, in the pyramidal layer of the hippocampus, enhanced the population spike (s) evoked by fimbrial stimulation. In contrast, muscarinic and nicotinic agents had an opposite action on on the dendritic field potentials, they respectively reduced and enhanced the negative fields (field EPSP) recorded in the apical dendrites. These effects were antagonized by muscarinic and nicotinic antagonists, respectively.
A simple method for implanting cortical and subcortical electrodes in very young rats is described, which does not interfere with the behavior of the animal during the experiment. The cortical electrodes are anchored to the skull by a spiral whose first loop is introduced between the inner layer of the skull and the dura mater. The subcortical electrodes have a loop which rests above the skull. Both the spirals of the cortical electrodes and the loops of subcortical electrodes are then embedded in dental acrylic.
The amplitude modifications of VERs from paired geniculate stimuli during paradoxical sleep were studied in five cats with chronically implanted electrodes, in the presence of REMs and during PGOs without REMs. In both cases the C5 component of evoked potentials was significantly enhanced with respect to the controls. This facilitation affecting presumably only the postsynaptic component of the response seems linked to signals reaching the visual cortex through other than geniculo-striate pathways. The disinhibition of the second VER appears to be due to intracortical mechanisms, and is not specifically related to phasic events of sleep, such as we previously described during light conditioning and in the absence of eye movements. It is proposed that this effect may be a more general phenomenon caused by changes in cortical activation during eye movement and conditioning.
The action of glycine (Gly) intravenously injected on rat epileptic foci induced by strychnine or penicillin topically applied, was compared with that of GABA. Gly (450 mg/kg i.v.) produced a complete block of the spiking activity. The inhibitory action of GABA (80 mg/kg), in terms of threshold and duration, was stronger than the action of Gly. The same inhibitory effect was also observed if these amino acids were applied topically or intracisternally. These results are consistent with the possibility that Gly has a role in the rat cortical inhibition.
Simultaneous recordings of the EEG, the electromyogram of the small intestine, the electrocardiogram, and femoral arterial pressure were monitored in 24 cats anesthetized with halothane, immobilized with gallamine, and artificially respirated. During pentylenetetrazol-induced generalized seizures, intestinal activity was blocked, as demonstrated by the disappearance of spikes from the EMG. This block was abolished by spinal cord section at C1-C2 level and partially abolished by bilateral adrenalectomy. These results demonstrate the existence of inhibitory sympathetic mechanisms during generalized experimental seizures.
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The effects of unilateral medial forebrain bundle ("MFB") lesions on the spontaneous firing patterns of caudate neurons on both sides of the brain in cats were studied 3 days, 7 days and more than 2 weeks postlesion. Our results indicate that: (1) the spontaneous firing of neurons in the caudate nucleus ipsilateral to the lesion slows significantly by 3 days postlesion and returns to control values by 7 days postlesion, (2) the spontaneous activity of contralateral caudate neurons slows progressively with postlesion time and (3) these changes in neural activity are not correlated with changes in dopamine concentrations in the caudate nucleus.
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The actions of GABA and glycine (Gly), iontophoretically applied to rat cortical neurons, were compared. These amino acids hyperpolarized the membrane cell, decreasing the membrane resistance. The results show that the ionic mechanisms involved in the inhibitory actions of GABA and Gly are probably the same in contrast with the results obtained in cat cortical neurons.
Intracellular recordings were made from caudate neurons in anesthetized kittens of 2-72 days of age. In adult cats, results of intracellular recordings indicate that caudate neurons respond most frequently to stimulation of their major afferents from cortex, thalamus and substantia nigra with a sequence of excitation followed by inhibition (EPSP-IPSP sequence). The results of the present study show that the prominent IPSP of this sequence is not well developed in young kittens and does not reach adult values in terms of frequency of occurrence until beyond 40 days of age. Amplitude and duration of the IPSP evoked by cortical stimulation also did not reach adult values until beyond 40 days of age. In contrast, EPSPs can be evoked in the youngest kittens by stimulation of afferents to the caudate. These findings suggest that the caudate nucleus may alter its role during development. In early postnatal periods it functions as a simple relay system transmitting incoming information to its outputs in a relatively unaltered fashion. Later in development it becomes a system capable of complex modulation and filtering of neural information.
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