We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular-spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III-VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8-1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long-lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3-12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6-1 Hz) than under urethane anesthesia (0.3-0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15-30 Hz), relatively short-lasting (15-25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long-lasting hyperpolaryzations.(ABSTRACT TRUNCATED AT 400 WORDS)

The newly described slow cortical rhythm (approximately 0.3 Hz), whose depolarizing-hyperpolarizing components are analyzed in the preceding article, is now investigated from the standpoint of its relations with delta (1-4 Hz) and spindle (7-14 Hz) rhythmicity. Regular-spiking and intrinsically bursting cortical neurons were mostly recorded from association suprasylvian areas 5 and 7; fewer neurons were also recorded from pericruciate motor and posterolateral visual areas. Although most cells were investigated under various anesthetics, a similar slow cortical rhythm was found in animals with brainstem transection at the low- or high-collicular levels. These cerveau isolé (isolated forebrain) preparations display the major sleep rhythms of the EEG in the absence of general anesthetics. In 38% of recorded cortical neurons (n = 105), the slow rhythm was combined with delta oscillation. Both cellular rhythms were phase locked to the slow and delta oscillations in the surface- and depth-recorded EEG. In a group of this cell sample (n = 47), delta activity occurred as stereotyped, clock-like action potentials during the interdepolarization lulls of the slow rhythm. In another neuronal subsample (n = 58), delta events were grouped in sequences superimposed upon the depolarizing envelope of the slow rhythm, with such sequences recurring rhythmically at approximately 0.3-0.4 Hz. The associations between the two cellular and EEG rhythms (1-4 Hz and 0.3-0.4 Hz) were quantified by means of autocorrelograms, cross-correlograms, and spike-triggered averages. In 26% of recorded neurons (n = 72), the slow rhythm was combined with spindle oscillations. Regular-spiking cortical neurons fully reflected the whole frequency range of thalamically generated spindles (7-14 Hz). However, during similar patterns of EEG spindling, intrinsically bursting cells fired grouped action potentials (with intraburst frequencies of 100-200 Hz) at only 2-4 Hz. The dependence of the slow cortical oscillation upon the thalamus was studied by lesions and stimulation. The slow rhythm survived extensive ipsilateral thalamic destruction by means of electrolytic lesions or kainate-induced loss of perikarya in thalamic nuclei that were input sources to the recorded cortical neurons. To further prevent the possibility of a thalamic role in the genesis of the slow rhythm, through the contralateral thalamocortical systems and callosal projections, we also transected the corpus callosum in thalamically lesioned animals, and still recorded the slow rhythm in cortical neurons. These data indicate that the thalamus is not essentially implicated in the genesis of the slow rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)

Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation. Furthermore, systemic injection of IGF-I mimicked the effects of exercise in the brain. Thus, brain uptake of IGF-I after either intracarotid injection or after exercise elicited the same pattern of neuronal accumulation of IGF-I, an identical widespread increase in neuronal c-Fos, and a similar stimulation of hippocampal brain-derived neurotrophic factor. When uptake of IGF-I by brain cells was blocked, the exercise-induced increase on c-Fos expression was also blocked. We conclude that serum IGF-I mediates activational effects of exercise in the brain. Thus, stimulation of the uptake of blood-borne IGF-I by nerve cells may lead to novel neuroprotective strategies.

As most afferent axons to the thalamus originate in the cerebral cortex, we assumed that the slow (< 1 Hz) cortical oscillation described in the two companion articles is reflected in reticular (RE) thalamic and thalamocortical cells. We hypothesized that the cortically generated slow rhythm would appear in the thalamus in conjunction with delta and spindle oscillations arising from intrinsic and network properties of thalamic neurons. Intracellular recordings have been obtained in anesthetized cats from RE (n = 51) and cortically projecting (n = 240) thalamic neurons. RE cells were physiologically identified by cortically evoked high-frequency spike bursts and depolarizing spindle oscillations. Thalamocortical cells were recognized by backfiring from appropriate neocortical areas, spindle-related cyclic IPSPs, and hyperpolarization-activated delta oscillation consisting of rhythmic low-threshold spikes (LTSs) alternating with afterhyperpolarizing potentials (AHPs). The slow rhythm (0.3-0.5 Hz) was recorded in 65% of RE neurons. In approximately 90% of oscillating cells, the rhythm consisted of prolonged depolarizations giving rise to trains of single action potentials. DC hyperpolarization increased the synaptic noise and, in a few cells, suppressed the long-lasting depolarizing phase of the slow rhythm, without blocking the fast EPSPs. In approximately 10% of oscillating neurons, the hyperpolarizing phase of the oscillation was much more pronounced, thus suggesting that the slow rhythm was produced by inhibitory sculpturing of the background firing. The slow oscillation was associated with faster rhythms (4-8 Hz) in the same RE neuron. The slow rhythm of RE neurons was closely related to EEG wave complexes recurring with the same frequency, and its strong dependency upon a synchronized state of cortical EEG was observed during shifts in EEG patterns at different levels of anesthesia. In 44% of thalamocortical cells the slow rhythm of depolarizing sequences was apparent and it could coexist with delta or spindle oscillations in the same neuron. The occurrence of the slowly recurring depolarizing envelopes was delayed by the hyperpolarizing spindle sequences or by the LTS-AHP sequences of delta oscillation. The hyperpolarization-activated delta potentials that tended to dampen after a few cycles were grouped in sequences recurring with the slow rhythm. We finally propose a unified scenario of the genesis of the three major sleep rhythms: slow, delta, and spindle oscillations.

In vivo and in vitro studies reveal that astrocytes, classically considered supportive cells for neurons, regulate synaptic plasticity in the mouse hippocampus and are directly involved in information storage.