Characterization of the 7-12 Hz EEG oscillations during immobile waking and REM sleep in behaving rats.

OBJECTIVE: The aim of this study was to examine whether the mu rhythm is also seen in the EEG of alert, undrugged and freely moving rats. The mu rhythm is a salient neocortical synchrony with dominant frequency in the 8-13 Hz band, initially recorded over the parietal and frontal areas of humans and subsequently investigated in monkeys and cats using the term sensorimotor rhythm. In the rat, these oscillations have been described only at single-unit level in the trigeminal system or in the cerebellar hemispheres. METHODS: In order to identify this rhythm, according to the "functional topography" approach, we examined the shape, spectral content, spatial distribution in power spectra, and functional reactivity. Rats were implanted with multiple electrodes along the antero-posterior axes. Monopolar recordings and simultaneous continuous 24-h video were taken in natural dark-light cycles for 6 consecutive days. Brain mappings based on quantitative spectral analysis were made. RESULTS: Spontaneous well-defined 7-12 Hz EEG oscillations were found during immobile wakefulness and REM sleep. Comparable features of these patterns indicated that they are largely analogous to the mu rhythm. CONCLUSIONS: The conservation of mu rhythm in the EEG across mammalian species with different cortical extension suggests that it is functionally important. SIGNIFICANCE: Given the great interest aroused by the properties of the mirror neurons, reflected by the mu rhythm, the detailed characterization of this rhythm in rats during natural life may prove useful in prospective evolutionary studies.

Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged freely-moving rats.

In chronically-implanted, drug-free, behaving aged Fischer rats, intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) acetyl-L-carnitine (ALCAR) injections powerfully enhanced motor behavior and head movements aimed at attention and exploratory activity. This effect was dose-dependent and associated with the abolition or substantial reduction of the incidence and duration of the spontaneous EEG generalized hypersynchronous patterns termed High Voltage Spindle (HVS), with an increase in EEG monitored theta activity. The results suggest that ALCAR may stimulate the motivational system and disrupt the hypersynchronous processes by inhibiting the GABAergic thalamic reticular neurons and/or activating the brain stem cholinergic reticular system (pedunculo pontine tegmental, PPT and laterodorsal tegmental, LDT nuclei).

The dream between neuroscience and psychoanalysis.

The dream is tackled sometimes from the neurobiological viewpoint, sometimes from the neuropsychological angle, or from the positions of experimental and psychoanalytical psychology. Interest in dreams started with psychoanalysis in 1900, and 53 years later the discovery of REM sleep by Aserinski and Kleitman, and subsequent psychophysiological findings took the dream into the realm of biology. The dichotomous model of REM and non-REM sleep is described, as a basis for thought-like activity (non-REM sleep) and dreaming (REM sleep). This led to Hobson and McCarley's theory of activation-synthesis, suggesting that the mind while dreaming is simply the brain self-activated in REM sleep. Psychophysiological research has shown that people dream in all phases of sleep, from falling asleep to waking, but that the characteristics of the dreams may differ in the different phases. Bio-imaging studies indicate that during REM sleep there is activation of the pons, the amygdala bilaterally, and the anterior cingulate cortex, and disactivation of the posterior cingulate cortex and the prefrontal cortex. The images suggest there is a neuroanatomical frame within which dreams can be generated and then forgotten. Psychoanalysis studies the dream from a completely different angle. Freud believed it was the expression of hallucinatory satisfaction of repressed desires. Today it is interpreted as the expression of a representation of the transference in the hic et nunc of the session. At the same time it also has symbol-generating functions which provide an outlet by which affective experiences and fantasies and defences stored as parts of an unrepressed unconscious in the implicit memory can be represented in pictorial terms, then thought and rendered verbally. From the psychoanalytical point of view, the dream transcends neurobiological knowledge, and looks like a process of internal activation that is only apparently chaotic, but is actually rich in meanings, arising from the person's affective and emotional history.

Spontaneous K-complexes in behaving rats.

The K-complex (KC) is an electrographic rhythmic pattern present in human and cat sleep EEG. In long-term multisite videoEEG recordings in behaving Sprague-Dawley (SD) rats, well-defined spontaneous KCs were observed during sleep. Sprague-Dawley rats were implanted with multiple electrodes bilaterally along the antero-posterior axes at the locations F1, F2, F7, F8, T3, T4, P3, P4, all against a ground reference placed in the midline above the cerebellum. Multiple, closely spaced cortical electrodes allowed two-dimensional surface brain mapping of the power spectra distribution. Two silver wires were also inserted into nuchal muscles to record EMG activity. Each rat was monopolarly recorded from 0900 h to 1500 h in a natural dark-light rodents, we examined the patterns of appearance in various conditions, the progression through a full sleep-waking cycle, the shape, density, spectral components, and spatial distribution in power spectra. The rat KC appears to share similar features with the human and cat KC.

Thalamocortical dysrhythmia and the thalamic reticular nucleus in behaving rats.

OBJECTIVES: The aim of this study was to investigate the effects of bilateral chemical lesion of the rostral pole of the thalamic reticular nucleus on EEG activities in freely moving rats applying quantitative analysis and brain mapping of power spectra distribution. METHODS: Ketamine-sedated Sprague-Dawley rats were implanted to monitor behavioral states with frontoparietal electrodes in a first series of experiments and with multiple electrodes along the antero-posterior axis (F1, F2, F7, F8, T3, T4, P3, P4) in a second series. Monopolar and bipolar recordings were obtained in animals stereotaxically injected with ibotenic acid into both rostral poles of the thalamic reticular nucleus. Long-term video-EEG recordings and brain mapping based on quantitative spectral analysis were made. RESULTS: Two forms of dysrhythmia gradually emerged in the neocortical EEG at 12-24h post-injection: potentiation of theta waves and spontaneous high-voltage spindles (HVS) at 4.5-8Hz frequency. Brain mapping during these dysrhythmia shows highest power posteriorly (parietotemporal) for theta and mesiofrontally for HVS. CONCLUSIONS: Given the lack of inhibitory intrinsic interneurons in the rat thalamus, bilateral destruction of a small part of the solely GABAergic population may promote cortical dysrhythmia (probably by dis-inhibition). The topographic differences in power might indicate different involved structures.

Sleep is differently modulated by basal forebrain GABA(A) and GABA(B) receptors.

There is evidence that GABA plays a major role in sleep regulation. GABA(A) receptor agonists and different compounds interacting with the GABA(A) receptor complex, such as barbiturates and benzodiazepines, can interfere with the sleep/wake cycle. On the other hand, there is very little information about the possible role of GABA(B) receptors in sleep modulation. The nucleus basalis of Meynert (NBM), a cholinergic area in the basal forebrain, plays a pivotal role in the modulation of sleep and wakefulness, and both GABA(A) and GABA(B) receptors have been described within the NBM. This study used unilateral infusions in the NBM to determine the effects of 3-hydroxy-5-aminomethylisoxazole hydrobromide (muscimol hydrobromide, a GABA(A) receptor subtype agonist) and beta-(aminomethyl)-4-chlorobenzenepropanoic acid (baclofen, a GABA(B) receptor subtype agonist) on sleep parameters in freely moving rats by means of polygraphic recordings. Muscimol (0.5 nmol) and baclofen (0.7 nmol) induced an increase in slow-wave sleep and an inhibition of wakefulness. Muscimol, but not baclofen, also caused a decrease in desynchronized sleep parameters. The results reported here indicate that 1) the NBM activation of both GABA(A) and GABA(B) receptors influences the sleep/wake cycle, and 2) GABA(A) but not GABA(B) receptors are important for desynchronized sleep modulation, suggesting that the two GABAergic receptors play different roles in sleep modulation.

The synchronizing influence of Substantia Innominata on the thalamus of the cat.

We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the waking state, on the 'central' part of the Mediodorsal nucleus of the thalamus (MD), combining electrophysiological and anatomical techniques in restrained, undrugged, unanaesthetized cats. Thalamic MD units were recorded, after electrical stimulation of the Substantia Innominata, at 1 Hz, with a single pulse or short trains of four pulses. Responses were studied by poststimulus histograms. In about 64 of the 84 recorded MD neurones (76%), stimulation of the Substantia Innominata, during the waking state, induced a brief cell excitation, followed first by prolonged inhibition of firing and then by a strong excitatory rebound discharge; after this comes a second sequence of inhibition and excitation, of decreasing amplitude. After stimulation of the Substantia Innominata, the MD units tended to start a repetitive discharge at 4--7 Hz. To investigate the connections of Substantia Innominata cells upon the areas where MD units were recorded we injected horseradish peroxidase wheat germ agglutinin (WGA-HRP), combined with immunohistochemistry for glutamic acid decarboxylase (GAD) and choline acetyl transferase (ChAT). Of the total population of retrogradely labelled cells in the Substantia Innominata 53% were GAD positive while less than 16% were ChAT positive. The GAD positive MD-projecting cells in the Substantia Innominata were triangular to fusiform and small to medium in size. These findings indicate that GABAergic input from the Substantia Innominata may contribute to increasing the hyperpolarizing inhibitory pressure on MD cells in the 'central' part during slow wave sleep (SWS).

Effects of bilateral microinjections of ibotenic acid in the thalamic reticular nucleus on delta oscillations and sleep in freely-moving rats.

The thalamic reticular nucleus (NRT) consists of a large pool of GABAergic neurons located on each side on the anterior, lateral, and ventral surfaces of the dorsal thalamus. The NRT is divided up into sectors. The aim of this study was to investigate the effects of bilateral lesions of the NRT on sleep and sleep oscillations. Only the results concerning delta oscillations will be reported here. As a first step we produced stereotaxically placed electrolytic lesions. The rats presented continuous circling behavior with electroencephalographic (EEG) theta and delta activity and subsequent sudden death. To avoid disruption of the bundles of fibers that pass through the NRT to and from the cerebral cortex, we used the excitotoxic ibotenic acid. Given its high toxicity, we concentrated on the rostral pole of the NRT, which is believed to have powerful effects on the synchronization of oscillatory activity during sleep. Immediately after surgery, the rats fell into a deep sleep during which there was an increase in EEG slow-wave activity and no spindles. On postoperative day 2, corresponding to the destruction period, the sleep/wake cycle partially recovered, but NREM sleep was quantitatively diminished and showed abnormalities (increased latency to sleep onset, sleep fragmentation, gradual elimination of the delta rhythm). It is concluded that the rostral pole of the NRT contributes to normal and pathological EEG synchronization and the organization of sleep in rats.

5-Hydroxytryptophan, but not L-tryptophan, alters sleep and brain temperature in rats.

The precise role of serotonin (5-hydroxytryptamine) in the regulation of sleep is not fully understood. To further clarify this role for 5-hydroxytryptamine, the 5-hydroxytryptamine precursors L-tryptophan (40 and 80 mg/kg) and L-5-hydroxytryptophan (25-, 50-, 75-, 100 mg/kg) were injected intraperitoneally into freely behaving rats 15 min prior to dark onset, and subsequent effects on sleep-wake activity and cortical brain temperature were determined. L-5-hydroxytryptophan, but not L-tryptophan, induced dose-dependent changes in sleep-wake activity. During the 12-h dark period, non-rapid eye movement sleep was inhibited in post-injection hours 1-2 by the two lowest L-5-hydroxytryptophan doses tested, while the two highest doses induced a delayed increase in non-rapid eye movement sleep in post-injection hours 3-12. These highest doses inhibited non-rapid eye movement sleep during the subsequent 12-h light period. The finding that L-5-hydroxytryptophan, but not L-tryptophan, induced a dose-dependent and long-lasting decrease in cortical brain temperature regardless of whether or not non-rapid eye movement sleep was suppressed or enhanced contributes to a growing list of conditions showing that sleep-wake activity and thermoregulation, although normally tightly coupled, may be dissociated. The initial non-rapid eye movement sleep inhibition observed following low doses of L-5-hydroxytryptophan may be attributable to increased serotonergic activity since 5-hydroxytryptamine may promote wakefulness per se, whereas the delayed non-rapid eye movement sleep enhancement after higher doses may be due to the induction by 5-hydroxytryptamine of sleep-inducing factor(s), as previously hypothesized. The period of non-rapid eye movement sleep inhibition beginning 12 h after administration of L-5-hydroxytryptophan doses that increase non-rapid eye movement sleep is characteristic of physiological manipulations in which non-rapid eye movement sleep is enhanced. The results of the present study suggest that the complex effects of 5-HT on sleep depend on the degree and time course of activation of the serotonergic system such that 5-HT may directly inhibit sleep, yet induce a cascade of physiological processes that enhance subsequent sleep.

Kant's philosophy and its relationship with the thought of Bion and Money-Kyrle.

The authors assess the significance of the rediscovery of Kant's philosophy of mind, which in their view offers valuable insights into the basis of conscious and unconscious mental life, protomental structures and the organisation of the internal world. They draw attention to the importance of distinguishing between brain culture, as represented by the neurosciences in particular, and mind culture. The process of internalisation begun by Kant is stated to have been continued by present-day psychoanalysis, whose theories furnish some additional categories of the intellect. The ideas of Bion and Money-Kyrle are considered in the light of Kantian philosophy. The authors show how Kant's revolutionary shift from enquiring into things to enquiring into our mode of knowing them implied that the objects of experience were determined by the transcendental functions of the mind, seen as a priori elements. Space and time as pure intuitions, together with the categories of the intellect organised by the 'I think', were held by Kant to make knowledge possible. Noting that the unconscious is not to be equated with the Kantian noumenon, the authors contend that Kant's epistemology can help psychoanalysis today to reflect on the epistemic status of its own referent, the conscious and unconscious mind, as well as of its procedures and predicates.

Stimulation of NMDA and AMPA receptors in the rat nucleus basalis of Meynert affects sleep.

The nucleus basalis of Meynert (NBM), a heterogeneous area in the basal forebrain involved in the modulation of sleep and wakefulness, is rich in glutamate receptors, and glutamatergic fibers represent an important part of the input to this nucleus. With the use of unilateral infusions in the NBM, the effects of two different glutamatergic subtype agonists, namely N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) hydrobromide, on sleep and wakefulness parameters were determined in freely moving rats by means of polygraphic recordings. NMDA (5 nmol) and AMPA (0.4 nmol) induced an increase in wakefulness and an inhibition of slow-wave sleep. AMPA, but not NMDA, also caused a decrease in desynchronized sleep. These AMPA- and NMDA-mediated effects were counteracted by a pretreatment with the specific NMDA antagonist 2-amino-5-phosphonopentanoic acid (20 nmol) and the specific AMPA antagonist 6,7-dinitroquinoxaline-2,3-dione (2 nmol), respectively. The results reported here indicate that 1) the NBM activation of both NMDA and AMPA glutamate receptors exert a modulatory influence on sleep and wakefulness, and 2) AMPA, but not NMDA receptors, are involved in the modulation of desynchronized sleep, suggesting a different role for NBM NMDA and non-NMDA receptors in sleep modulation.

Blockade of 5-hydroxytryptamine (serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep.

Recent data suggest that interleukin-1-induced enhancement of non-rapid eye movement sleep is mediated, in part, by the serotonergic system. To determine if sleep changes induced by interleukin-1 are mediated by a specific serotonergic receptor subtype, we evaluated interleukin-1 effects on sleep in rats pretreated with the 5-hydroxytryptamine (serotonin)-2 receptor antagonist ritanserin. Ritanserin (0.63 mg/kg, intraperitoneally) by itself did not alter sleep-wake behavior, although it did reduce cortical brain temperature. Interleukin-1 (5 ng, intracerebroventricularly) enhanced non-rapid eye movement sleep, suppressed rapid eye movement sleep, and induced a moderate febrile response. Pretreatment with ritanserin completely blocked the febrile response to interleukin-1 and abolished the interleukin-1-induced enhancement in non-rapid eye movement sleep that occurred during postinjection hours 3-4, without altering interleukin-1 effects on rapid eye movement sleep. The present data suggest that serotonin may partially mediate interleukin-1 effects on sleep by interacting with 5-hydroxytryptamine (serotonin)-2 receptors. These results also suggest that interactions between the serotonergic system and interleukin-1 may be important in regulating sleep-wake behavior.

Hypothalamic serotonergic activity correlates better with brain temperature than with sleep-wake cycle and muscle tone in rats.

The activity of the serotonergic system varies in phase with the sleep-wake cycle, which is associated with changes in several physiological functions, including electroencephalographic activity, brain temperature, and locomotion. The aim of the present study was to clarify which of these parameters correlates better with serotonergic activity in spontaneous conditions. Voltammetric recordings by telemetry of serotonergic metabolism in the medial preoptic area and polygraphic recordings of sleep-wake activity (by means of electroencephalographic delta band, brain cortical temperature and neck electromyographic activity recordings) were simultaneously performed in freely moving rats. Univariate analyses of variance revealed that each variable under investigation was statistically correlated with serotonergic metabolism. When the variables were entered into the model simultaneously, both partial correlation and step-wise multiple regression analyses indicated that the highest correlation exists between serotonergic metabolism and brain cortical temperature. The present data show that serotonergic activity in the medial preoptic area is closely linked to physiological changes in brain temperature.

Hippocampal type 1 (movement-related) theta rhythm positively correlates with serotonergic activity.

To investigate the relationship between the hippocampal [symbol: see text] activity (or Rhythmical Slow Activity, RSA) and the hippocampal serotonergic activity during spontaneous behavior, simultaneous recordings of i) hippocampal EEG, ii) sleep-wake activity, and iii) hippocampal levels of the serotonin (5-HT) metabolite 5-hydroxyndolacetic acid (5-HIAA--measured by in vivo voltammetry and infrared telemetry) were performed. The results show that hippocampal type 1 RSA recorded during wakefulness and voluntary movements (such as walking), is positively correlated to hippocampal 5-HIAA levels. Since in the experimental conditions used in the study, 5-HIAA levels are a reliable index of 5-HT release, the results support the hypothesis that hippocampal type 1 RSA is generated by a serotonergic mechanism. In contrast, hippocampal type 2 RSA recorded during desynchronized sleep is negatively correlated with 5-HT release, suggesting a different neurochemical mechanism for its production. These results also show that, in the experimental condition of this study, hippocampal RSA power spectrum has a main peak frequency of 3.5 during wakefulness, and of 6.5 Hz during desynchronized sleep.

Psychoanalysis and the neurosciences: a topical debate on dreams.

The author begins by pointing out that, whereas Freud first turned his attention to dreams in 1895, they became an object of neuroscientific interest only in the 1950s, after the discovery of rapid-eye-movement (REM) sleep and the observation that a subject woken in an REM phase could remember and narrate them. He discusses the various brain structures found by the neuroscientists to be implicated in dreaming and the associated hypotheses about their involvement in the processes of remembering dreams, their spatial construction and semantic organisation, and the dreamer's emotional participation in and narration of dreams. Attention is drawn to recent psychophysiological research findings indicating that dreaming occurs in all sleep phases and not only in REM episodes. The cognitivist contribution is also discussed. The author goes on to demonstrate the difference between the neuroscientific and psychoanalytic approaches to dreams. Whereas the neuroscientists are interested in the structures involved in dream production and in dream organisation and narratability, psychoanalysis concentrates on the meaning of dreams and on placing them in the context of the analytic relationship in accordance with the affective history of the dreamer and the transference. The brain structures and functions of interest to the neurosciences, while constituting the physical and biological substrate of these aspects, are stated to be irrelevant to their psychoanalytic understanding.

GABAergic and cholinergic basal forebrain and preoptic-anterior hypothalamic projections to the mediodorsal nucleus of the thalamus in the cat.

The present study examined projections of GABAergic and cholinergic neurons from the basal forebrain and preoptic-anterior hypothalamus to the "intermediate" part of the mediodorsal nucleus of the thalamus. Retrograde transport from this region of the mediodorsal nucleus was investigated using horseradish peroxidase-conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase immunohistochemical staining for glutamic acid decarboxylase and choline acetyltransferase. A relatively large number of retrogradely-labelled glutamic acid decarboxylase-positive neurons are located in the basal forebrain, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. Moreover, retrogradely-labelled choline acetyltransferase-positive cells are interspersed among glutamic acid decarboxylase-positive neurons, accounting for about 6% of the total choline acetyltransferase-positive cell population in the basal forebrain. The glutamic acid decarboxylase-positive and choline acetyltransferase-positive retrogradely-labelled neurons are distributed throughout several regions of the basal forebrain, including the medial septum, the diagonal band of Broca, the magnocellular preoptic nucleus, the substantia innominata pars anterior, the substantia innominata pars posterior, and the globus pallidus where only a few retrogradely-labelled neurons were seen. The choline acetyltransferase-positive mediodorsal-projecting neurons are morphologically different from the choline acetyltransferase-positive neurons in the basal forebrain, suggesting that those projecting to the mediodorsal nucleus are a small proportion of the cholinergic neuronal population in the basal forebrain. In the preoptic-anterior hypothalamus, many retrogradely-labelled glutamic acid decarboxylase-positive cells were found, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. These retrogradely-labelled glutamic acid decarboxylase-positive neurons are distributed throughout the preoptic-anterior hypothalamus in a continuous line with those in the basal forebrain, including the lateral preoptic area, the medial preoptic area, the bed nucleus of the stria terminalis, and the anterior and dorsal hypothalamic areas. The highest percentage of mediodorsal-projecting GABAergic neurons is in the anterior lateral hypothalamus where more than 25% of the total population of glutamic acid decarboxylase-positive cells project to the mediodorsal nucleus of the thalamus. Overall, of the large population of retrogradely-labelled neurons in the basal forebrain and preoptic-anterior hypothalamus, a significant proportion are glutamic acid decarboxylase-positive neurons (> 60% in the basal forebrain and > 30% in the preoptic-anterior hypothalamus), while the choline acetyltransferase-positive neurons amount to a smaller percentage of the neurons projecting to the mediodorsal nucleus (< 13% in the basal forebrain and < 2% in the preoptic-anterior hypothalamus). These results provide anatomical evidence of direct GABAergic projections from the basal forebrain and preoptic-anterior hypothalamic regions to the "intermediate" part of the mediodorsal nucleus in the cat. This GABAergic projection field could be the direct pathway by which the basal forebrain directly modulates thalamic excitability and may also be involved in mechanisms modulating electroencephalographic synchronization and sleep through the "intermediate" mediodorsal nucleus.

Multiple modulatory effects of dopamine on calcium channel kinetics in adult rat sensory neurons.

1. The aim of this research was to study the modulatory effects induced on high-voltage-activated (HVA) calcium channels and pharmacologically isolated subtypes through dopamine receptor activation. 2. The experiments were carried out on acutely isolated adult rat sensory neurons, recorded by means of the whole-cell patch-clamp technique. 3. At saturating concentrations dopamine was effective in inducing: (a) a voltage-dependent prolongation of activation kinetics, (b) a voltage-independent scaling down of the currents without any changes in activation and inactivation kinetics, and (c) an acceleration of inactivation kinetics, not affected by a positive conditioning prepulse. 4. These three inhibitory effects were observed on N- and P/Q-type currents, whereas only a voltage-independent scaling up and/or scaling down was observed on L-type current. 5. The inhibitory effects were sometimes observed in isolation in different neurons, but more frequently they were variously combined in the same cell. A correlation analysis of these effects shows no relationship between them, corroborating the conclusion that they are mechanistically distinct. 6. The existence of an inactivating effect accounts for the occurrence of a voltage-dependent inhibitory effect in some cells without an apparent slowing down of activation kinetics, since the increased inactivation may mask the slow component of the activation. 7. The multiple modulatory effects on calcium channels, even on pharmacologically separated N-, L- and P/Q-currents, suggest that pharmacological and functional classifications do not necessarily match completely. 8. The multiple modulatory effects on HVA calcium currents may play a prominent role both in controlling the integrative properties of neurons and in regulating output at a presynaptic level.

Abolition of the neocortically monitored theta rhythm after ibotenic acid lesion of the parafascicular nucleus in behaving rats.

Seven adult Sprague-Dawley rats, chronically implanted with standard electrodes to monitor frontoparietal electroencephalographic (EEG) and nuchal electromyographic (EMG) activity, received, under deep anesthesia, unilateral or bilateral microinjections of ibotenic acid in the lateral part of the parafascicular nucleus of the thalamus. Four days after the injections (corresponding to the period of neuronal destruction), obliteration of the oscillatory activity in the theta range was found on the side ipsilateral to the injection, while on the intact hemisphere the rhythm was well developed. The asymmetry between the two hemispheres was particularly evident during REM sleep but was also seen during attentive but immobile alertness. In bilaterally injected rats, the neocortical theta rhythm was abolished on both hemispheres. These results suggest that in freely-moving rats the lateral parafasciculus neurons are part of the network on which the emergence of the theta rhythm relies.

Muramyl dipeptide and IL-1 effects on sleep and brain temperature after inhibition of serotonin synthesis.

The role of the interactions between serotonin (5-HT) and muramyl dipeptide (MDP) and interleukin-1 (IL-1) in sleep control and thermoregulation was evaluated. To this purpose, MDP and IL-1 were injected intracerebroventricularly at dark onset into freely moving rats pretreated twice intraperitoneally with para-chlorophenylalanine (PCPA) (300 mg/kg), which depletes brain 5-HT and causes insomnia. Fever and slow-wave sleep (SWS) enhancement induced by 150 pmol MDP were completely blocked in PCPA-pretreated rats. Only the first phase of the biphasic increase in SWS induced by 2.5 ng IL-1 was suppressed by PCPA pretreatment, whereas fever remained unaffected. These results suggest that 1) MDP effects on both sleep-wake activity and brain cortical temperature are mediated by the serotonergic system; 2) the mechanisms mediating the first and the second phases of IL-1-induced SWS excess are different: 5-HT could be involved in the first phase, but not in the second one; and 3) the 5-HT system does not appear to be involved in IL-1-induced fever.

GABAergic and other noncholinergic basal forebrain neurons, together with cholinergic neurons, project to the mesocortex and isocortex in the rat.

The extrathalamic relay from the brainstem reticular formation to the cerebral cortex in the basal forebrain has been thought to be constituted predominantly, if not exclusively, by cholinergic neurons. In contrast, the septohippocampal projection has been shown to contain an important contingent of gamma-aminobutyric acid (GABA)ergic neurons. In the present study, we investigated whether GABAergic neurons also contribute to the projection from the basal forebrain to neocortical regions, including the mesocortex (limbic) and the isocortex in the rat. For this purpose, retrograde transport of cholera toxin (CT) was examined from the medial prefrontal cortex for the mesocortex and from the parietal cortex for the isocortex and was combined with dual-immunohistochemical staining for either choline acetyltransferase (ChAT) or glutamic acid decarboxylase (GAD) in adjacent series of sections. Retrogradely labelled GAD+ neurons were codistributed with retrogradely labelled ChAT+ neurons through the basal forebrain from both the prefrontal and the parietal cortex, suggesting parallel, widespread cortical projections. The GAD+ cortically projecting cells were similar in size to the ChAT+ cells, thereby indicating that they comprise a contingent of the magnocellular basal cell complex. The proportions of retrogradely labelled neurons that were GAD+ (approximately one-third) were equal to or greater than those that were ChAT+ from both the prefrontal cortex and the parietal cortex. In addition, the total of GAD+ and ChAT+ neurons did not account for the total number of cortically projecting cells, indicating that another equivalent proportion of chemically unidentified noncholinergic neurons also contributes to the basalocortical projection. Accordingly, as in the allocortex, GABAergic, cholinergic, and other unidentified noncholinergic neurons may have the capacity to modulate activity in the mesocortex (limbic) and the isocortex through parallel, widespread projections.