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PubMed1975

Serotonin nerve terminals in adult rat neocortex.

Axonal processes which take up and retain exogenous tritiated serotonin ([3H]5-HT) have been demonstrated in the fronto-parietal cortex of adult rats, by means of high resolution radioautography. Prolonged topical superfusion with relatively high concentrations of ([3H]5-HT allowed detection of a maximal number of axonal reactions in the upper 3 layers of cortex. Comparison of results obtained from normal rats and animals pretreated with 6-hydroxydopamine or bearing midbrain raphe lesions established the specificity of this labeling. All reactive axons seemed to arise from the serotonin nerve cell bodies in groups B7 and B8 of Dahlström and Fuxe15. In electron microscope radioautographs, the serotonin fibers appeared as tenuous, naked axonal processes (0.1-0.5 mum in diameter) exhibiting small enlargements (0.7 mum in mean diameter) spaced at frequent intervals (1-3 mum). These boutons contained occasional mitochondria, small, round, agranular 'synaptic' vesicles and large granular vesicles. With axons, [3H]5-HT was concentrated in the boutons, and to a much lesser extent in connecting segments. This reactive pattern resembled that revealed by the fluorescence technique for endogenous serotonin. Preferential accumulations of the tracer by mitochondria and vesicular organelles indicated that these elements could sequester exogenous serotonin. Large granular vesicles were not necessarily visible in random thin sections of the labeled varicosities, and thus could not serve as the unique criterion for electron microscopic identification of 5-HT terminals. Moreover, these organelles are known to be present in other types of nerve endings. Topometric analysis of serial thin sections nevertheless demonstrated that large granular vesicles were potentially detectable in every 5-HT containing bouton, and also enabled extrapolation of their average number at 7 per varicosity. This low number makes it unlikely that large granular vesicles primarily represent storage sites. They could rather serve as a carrier for particle-bound enzymes essential to the local metabolism of serotonin or its precursors. A very small fraction of the serotonin varicosities exhibited the membrane differentiations of typical synaptic terminals. Extensive sampling in serial thin sections revealed junctional complexes in only 5% of labeled boutons, as opposed to 50% of unlabeled nerve endings in the surrounding neuropil. The data do not preclude the possibility that other monoaminergic neurons also share similar characteristics. It is probable that endogenous serotonin can be liberated from all axonal varicosities including those lacking strictu senso synaptic relationships. The overall configuration and ultrastructural features of cortical serotonin fibers suggest intrinsic dynamic properties which could assume particular significance in terms of function, plasticity and regrowth.

Animals↗
PubMed1975

Role of neocortex in binsural hearing in the cat. I. Contralateral masking.

Cats with earphones were trained with a shock avoidance procedure to detect the occurrence of 1 kHz tone pulses at one ear while continuous noise pulses were simultaneously presented to the opposite ear. For normal cats the presence of the noise produced a mean increase of 5.4 dB in the thresholds for detection of tones at the opposite ears. After large unilateral auditory cortex ablations the same cats exhibited an asymmetry between the ears in the size of the contralateral masking effect. There was a mean increase of 10.9 dB in the detection thresholds for tones at the ear contralateral to the damaged hemisphere when noise was presented to the ear opposite the intact hemisphere. Noise of the same physical intensity when presented to the ear contralateral to the damaged cortex produced no significant changes from the preoperative masking levels. Subsequent ablation of the auditory cortex of the opposite hemisphere resulted in a cancellation of the unilateral lesion effect; the cats exhibited interaurally symmetrical masking levels of the same magnitude as those observed prior to the first operation. Additional control tests indicate that the unilateral lesion effect is a central nervous system phenomenon and is specific to lesions of auditory cortex.

Animals↗
PubMed1975

Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats.

We measured simultaneously the oxidative metabolic activity, monitored as the tissue fluorescence attribute to intramitochondrial NADH, the extracellular potassium level with ion-selective microelectrodes, and the focal extracellular electrical potential, of one site in intact cerebral cortex of cats. When the cerebral was stimulated by trains of repeated electric pulses applied either directly to its surface or to an afferent pathway, the corrected cortical fluorescence (F-R) declined indicating oxidation of NADH, the activity of extracellular potassium [K+]o increased, and the extracellular potential (Vec) shifted in the negative direction. When mild to moderate stimuli not exceeding 10-15 sec in duration were used, a 3-fold correlation was found between these three variables. The regression of F-R over either Vec, or over log [K+]o had a positive ordinal intercept. The results are in agreement with earlier suggestions 4,24,25,43,45,46 that (a) much but not all the oxidative metabolic response of cortex to electrical stimulation is expended in restoring disturbed ion balance; and (b) that sustained shifts of potential (SP) in response to repetitive electrical stimulation are generated by glia cells depolarized by excess potassium. The magnitude of SP shifts associated with a given elevation of [k+]o are smaller in cerebral cortex than in spinal cord48,49. The correlation of F-R with [K+]o breaks down when pathologic processes of either seizure activity or spreading depression set in. During paroxysmal activity [K+]o tends to remain confined below 10-12 mM, a level observed in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing cortex as well, but oxidation of NADH progresses beyond that seen in non-convulsing tissue. This observation is hard to reconcile with the suggestion that excess potassium is a factor in the generation of seizures, at least of the type observed in this study. When [K+]o levels exceeded 10-12 mM, spreading depression invariably followed at least under the unanesthetized condition in these experiments. During spreading depression [K+]o levels rose to exceed 30 mM, sometimes 80 mM. NADH was oxidized during spreading depression to a level comparable to that seen in seizures. The observations are compatible with the suggestion13 that spreading depression occurs whenever the release of potassium into extracellular fluid is overloading its clearance therefrom.

Animals↗
PubMed1976

Role of neocortex in binaural hearing in the cat. II. The 'precedence effect' in sound localization.

The 'precedence effect' in sound localization refers to the situation in which two speakers, separated in space, emit identical sounds but one speaker leads by a few milliseconds. Normal observers perceive all the sound as originating from the leading speaker. In the present experiment cats were tested before and after unilateral ablation of auditory cortex on how well they could transfer a learned sound loclization response from situations involving unpaired sound sources to those with paired sources. Cats were tested with tone pairs separated by 5 msec and with clicks separated by delays of 3, 5, 7, 9, 12 and 16 msec. Preoperatively, the cats averaged 98% correct at a delay of 3 msec and 58% correct at 16 msec. Before surgery the probability of an error was independent of which speaker was leading; after surgery cats made significantly more errors when the leading speaker was located opposite the side of the lesion. Considerable individual variability was found with the 3 and 5 msec delay tests; some cats showed no evidence of a cortical deficit while others exhibited initial severe deficits which disappeared with training. At delays of 7-16 msec all cats showed severe directional deficits which were still present after 9 months of retraining. Results are interpreted as supporting the hypothesis that unilateral lesions disrupt binaural loudness rather than temporal relations.

Animals↗
PubMed1977

Electrically induced release of [3H]dopamine from slices obtained from different rat brain cortex regions. Evidence for a widespread dopaminergic innervation of the neocortex.

Slices obtained from the deeper layers of the rat dorsal frontal, parietal and occipital brain cortex were incubated in vitro with 6.25 X 10-7 M [3H]dopamine (DA), and subsequently superfused and electrically stimulated, while held on quick transfer electrodes, and changes in the efflux of 3H and of the individual amines measured. The separation of the amines, with quantitative recoveries, was performed by chromatography on cation-exchange resins eluted sequentially with water, 1 N HCL AND 6 M urea i 1 N HCl. When no drugs were used, the prestimulation efflux was entirely formed by deaminated metabolites, while following stimulation there was an increase in the efflux of deaminated metabolites, and considerable amounts of [3H]-noradrenaline (NA) now appeared. No DA was present in the pre- or poststimulation medium. Similar results were obtained in all the regions studied. When the slices were incubated with 10-5 M desmethylimipramine (DMI), 10-4 Mnialamide and 10-4 M tropolone, before and during incubation with [3H]DA, it was observed that, prior to stimulation, the efflux was composed of deaminated metabolites, DA and 3-methoxytyramine (MTA), and following the electrical stimulus there was an increased release of DA, NA and deaminated compounds (in order of decreasing release), while no change in that of MTA was evident. The stimulus-induced release of DA was greatest from frontal slices, intermediate from parietal, and lowest from occipital ones. DMI-resistant uptake of [3H]DA also diminished when passing from frontal to occipital. These findings are interpreted as due to the presence of dopaminergic axon terminals in all the regions studied, but with a density that diminishes in a rostrocaudal direction.

Adrenergic Fibers↗
PubMed1978

Operant conditioning of tonic firing patterns from precentral neurons in monkey neocortex.

This report presents a single neurons operant conditioning paradigm which allows the quantification of operant control between neurons and monkeys. The operant task is for the monkey to change firing patterns of the neuron from phasic to tonic. In 60 neurons conditioned after the protocol had been standardized the following results were obtained. (1) For a fixed interspike interval target range, the time off target may be considered error, and this may be used as a parameter with which to judge operant neuronal control. (2) The degree to which the monkey could control a neuron was not correlative with the neuron's initial firing rate, firing rate variance, or pattern. (3) Neurons coactivated by distal arm muscle groups were, as a group, more highly controlled in comparison to neurons coactivated by proximal muscle groups. (4) Pyramidal tract neurons, as a group, appear more accurately controlled than non-pyramidal tract neurons. (5) The role of proprioception in response acquisition is discussed.

Animals↗
PubMed1978

Epileptic and normal neurons in monkey neocortex: a quantitative study of degree of operant control.

The object of this study was to quantify and compare the degree of control monkeys may assert over firing patterns of normal and epileptic neurons. Thirty-seven epileptic and 70 normal neurons were studied in detail. The operant task was for the monkey to generate specified consecutive interspike intervals (ISI). The monkeys demonstrated far greater accuracy in controlling consecutive ISIs of normal neurons and were only able to control the intervals between bursts from epileptic neurons. The data implies that high frequency bursts of action potentials from epileptic neurons are all-or-nothing events initiated by synaptic mechanisms. In addition, some data are from a monkey with epilepsia partialis continua; in comparison to less active foci, this focus was comprised of a higher percentage of 'pacemaker' epileptic neurons.

Animals↗