Tegmental Nucleus Research Articles

Distribution of melanin-concentrating hormone-like immunoreactivity in the central nervous system of Rana esculenta

The distribution of salmon and rat melanin-concentrating hormone (MCH)-like and neuropeptide glutamate-isoleucine (NEI)-like immunoreactivity in the brain and spinal cord of the frog Rana esculenta was studied with immunohistochemistry. In the telencephalon, only fibers showed immunoreactivity in the olfactory bulb, lateral pallium, diagonal band, septum, and the amygdala. Immunoreactive fibers were abundant in all diencephalic structures, except the optic tract, the visual neuropils, and the habenula. Several cells in the central thalamic nucleus and a few in the suprachiasmatic nucleus were stained with the MCH antisera. Cells and their processes were intensely stained in the dorsal hypothalamus with the MCH and NEI antisera. Immunoreactive fibers were found in all tegmental nuclei and the white matter of the mesencephalon. They formed terminal plexuses in the deep layers of the optic tectum and the laminar nucleus of the torus semicircularis. Immunoreactive fibers were sparse in the rhombencephalon and the spinal cord.

Ascending and descending projections of the lateral vestibular nucleus in the frog Rana esculenta.

The lectin Phaseolus vulgaris leucoagglutinin was injected into the frog lateral vestibular nucleus (LVN) to study its antero- and retrograde projections. The following new observations were made. 1) In the diencephalon, vestibular efferents innervate the thalamus in a manner similar to that of mammalian species. The projections show a preference for the anterior, central, and ventromedial thalamic nuclei. 2) In the mesencephalon, vestibular fibers terminate in the tegmental nuclei and the nucleus of medial longitudinal fascicle. 3) In the rhombencephalon, commissural and internuclear projections interconnect the vestibular nuclei. Some of the termination areas in the reticular formation can be homologized with the mammalian inferior olive and the nucleus prepositus hypoglossi. Another part of the vestibuloreticular projection may transmit vestibular impulses toward the vegetative centers of the brainstem. A relatively weak projection is detected in the spinal nucleus of the trigeminal nerve, dorsal column nuclei, and nucleus of the solitary tract. 4) In the spinal cord, vestibular terminals are most numerous in the ipsilateral ventral horn and in the triangular area of the dorsal horn. 5) The coincidence of retrogradely labeled cells with vestibular receptive areas suggests reciprocal interconnections between these structures and the LVN. 6) In seven places, the LVN projections overlap the receptive areas of proprioceptive fibers, suggesting a convergence of sensory modalities involved in the sense of balance.

Theta synchronization in the limbic system: the role of Gudden's tegmental nuclei

European Journal of NeuroscienceVolume 13, Issue 2 p. 381-388 Theta synchronization in the limbic system: the role of Gudden's tegmental nuclei Bernat Kocsis, Bernat Kocsis Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, 74 Fenwood Rd, Boston, MA 02115, USA National Institute of Neurosurgery, Budapest, Hungary Center for Complex Systems, Florida Atlantic University, Boca Raton, FL, USASearch for more papers by this authorGonzalo Viana Di Prisco, Gonzalo Viana Di Prisco Center for Complex Systems, Florida Atlantic University, Boca Raton, FL, USASearch for more papers by this authorRobert Vertes, Robert Vertes Center for Complex Systems, Florida Atlantic University, Boca Raton, FL, USASearch for more papers by this author Bernat Kocsis, Bernat Kocsis Laboratory of Neurophysiology, Department of Psychiatry, Harvard Medical School, 74 Fenwood Rd, Boston, MA 02115, USA National Institute of Neurosurgery, Budapest, Hungary Center for Complex Systems, Florida Atlantic University, Boca Raton, FL, USASearch for more papers by this authorGonzalo Viana Di Prisco, Gonzalo Viana Di Prisco Center for Complex Systems, Florida Atlantic University, Boca Raton, FL, USASearch for more papers by this authorRobert Vertes, Robert Vertes Center for Complex Systems, Florida Atlantic University, Boca Raton, FL, USASearch for more papers by this author First published: 12 September 2011 https://doi.org/10.1111/j.1460-9568.2001.01392.xCitations: 16AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume13, Issue2January 2001Pages 381-388 RelatedInformation

Ontogeny of REM sleep in rats: possible implications for endogenous depression

Nine neonatal Long–Evans rats had continuous (24 h/day) polysomnography for 2 weeks, from age 14 days through age 27 days. A new finding was that six more or less independent measures of REM sleep occurrence decreased in parallel from age 14 days to age 27 days. The measures included parallel decreases of four measures of 24-h REM duration (tonic REM sleep, phasic REM sleep, mean REM period duration, and number of REM periods) along with parallel increases of two measures of REM delay (REM latency and percent of nonsleep onset REM periods). A parsimonious interpretation of the correlated changes is that a common developmental REM sleep inhibitory process accounts for the six parallel changes over time. This hypothesis can be tested empirically by studying inhibitory processes that operate on the pedunculopontine tegmental/latero-dorsal tegmental nuclei, the generators of REM sleep. The study also noted that compared with (same species) normal adults, endogenous depressives had the same distinctive REM sleep characteristics as neonatal rats. The similarity suggests that an underdeveloped, relatively weak REM sleep inhibitory process may account for the REM sleep peculiarities of endogenous depression. This hypothesis can be tested in adult rats made “depressed” by neonatal treatment with antidepressant drugs. Thus, the ontogeny of REM sleep suggests a developmental process that may be altered in humans predisposed to endogenous depression, and may account for the (life-long) REM sleep abnormalities of the disorder.

Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat

Orphanin FQ (OFQ) is the endogenous agonist of the opioid receptor-like receptor (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive of the opioid peptides. A cDNA encoding the OFQ precursor sequence in the rat recently has been cloned, and the authors recently generated a polyclonal antibody directed against the OFQ peptide. In the present study, the authors used in situ hybridization and immunohistochemistry to examine the distribution of OFQ peptide and mRNA in the central nervous system of the adult rat. OFQ immunoreactivity and prepro-OFQ mRNA expression correlated virtually in all brain areas studied. In the forebrain, OFQ peptide and mRNA were prominent in the neocortex endopiriform nucleus, claustrum, lateral septum, ventral forebrain, hypothalamus, mammillary bodies, central and medial nuclei of the amygdala, hippocampal formation, paratenial and reticular nuclei of the thalamus, medial habenula, and zona incerta. No OFQ was observed in the pineal or pituitary glands. In the brainstem, OFQ was prominent in the ventral tegmental area, substantia nigra, nucleus of the posterior commissure, central gray, nucleus of Darkschewitsch, peripeduncular nucleus, interpeduncular nucleus, tegmental nuclei, locus coeruleus, raphe complex, lateral parabrachial nucleus, inferior olivary complex, vestibular nuclear complex, prepositus hypoglossus, solitary nucleus, nucleus ambiguous, caudal spinal trigeminal nucleus, and reticular formation. In the spinal cord, OFQ was observed throughout the dorsal and ventral horns. The wide distribution of this peptide provides support for its role in a multitude of functions, including not only nociception but also motor and balance control, special sensory processing, and various autonomic and physiologic processes. J. Comp. Neurol. 406:503–547, 1999. © 1999 Wiley-Liss, Inc.

Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat

Orphanin FQ (OFQ) is the endogenous agonist of the opioid receptor-like receptor (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive of the opioid peptides. A cDNA encoding the OFQ precursor sequence in the rat recently has been cloned, and the authors recently generated a polyclonal antibody directed against the OFQ peptide. In the present study, the authors used in situ hybridization and immunohistochemistry to examine the distribution of OFQ peptide and mRNA in the central nervous system of the adult rat. OFQ immunoreactivity and prepro-OFQ mRNA expression correlated virtually in all brain areas studied. In the forebrain, OFQ peptide and mRNA were prominent in the neocortex endopiriform nucleus, claustrum, lateral septum, ventral forebrain, hypothalamus, mammillary bodies, central and medial nuclei of the amygdala, hippocampal formation, paratenial and reticular nuclei of the thalamus, medial habenula, and zona incerta. No OFQ was observed in the pineal or pituitary glands. In the brainstem, OFQ was prominent in the ventral tegmental area, substantia nigra, nucleus of the posterior commissure, central gray, nucleus of Darkschewitsch, peripeduncular nucleus, interpeduncular nucleus, tegmental nuclei, locus coeruleus, raphe complex, lateral parabrachial nucleus, inferior olivary complex, vestibular nuclear complex, prepositus hypoglossus, solitary nucleus, nucleus ambiguous, caudal spinal trigeminal nucleus, and reticular formation. In the spinal cord, OFQ was observed throughout the dorsal and ventral horns. The wide distribution of this peptide provides support for its role in a multitude of functions, including not only nociception but also motor and balance control, special sensory processing, and various autonomic and physiologic processes.

Injections of N-methyl-D-aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens

Injections of N-methyl-D-aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens

Injections of N‐methyl‐D‐aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens

Injections of N‐methyl‐D‐aspartate into the ventral hippocampus increase extracellular dopamine in the ventral tegmental area and nucleus accumbens

CNS pattern of metabolic activity during tonic pain: evidence for modulation by beta-endorphin.

CNS correlates of acute prolonged pain, and the effects of partial blockade of the central beta-endorphin system, were investigated by the quantitative 2-deoxyglucose technique in unanaesthetized, freely moving rats. Experiments were performed during the second, tonic phase of the behavioural response to a prolonged chemical noxious stimulus (s.c. injection of dilute formalin into a forepaw), or after minor tissue injury (s.c. saline injection). During formalin-induced pain, local glucose utilization rates in the CNS were bilaterally increased in the grey matter of the cervical spinal cord, in spinal white matter tracts and in several supraspinal structures, including portions of the medullary reticular formation, locus coeruleus, lateral parabrachial region, anterior pretectal nucleus, the medial, lateral and posterior thalamic regions, basal ganglia, and the parietal, cingulate, frontal, insular and orbital cortical areas. Pretreatment with anti-beta-endorphin antibodies, injected i.c.v., led to increased metabolism in the tegmental nuclei, locus coeruleus, hypothalamic and thalamic structures, putamen, nucleus accumbens, diagonal band nuclei and dentate gyrus, and in portions of the parietal, cingulate, insular, frontal and orbital cortex. In formalin-injected rats, pretreated with anti-beta-endorphin, behavioural changes indicative of hyperalgesia (increased licking response) were found, which were paralleled by a significant enhancement of functional activity in the anterior pretectal nucleus and in thalamo-cortical systems. A positive correlation was found between the duration of the licking response and metabolic activity of several forebrain regions. These results provide a map of the CNS pattern of metabolic activity during tonic somatic pain, and demonstrate a modulatory role for beta-endorphin in central networks that process somatosensory inputs.

Induction of Fos immunoreactivity by acute glucose deprivation in the rat caudal brainstem: relation to NADPH diaphorase localization.

Neuronal nitric oxide (NO) synthase, a NADPH diaphorase (NADPH-d) enzyme, catalyzes formation of the free radical neurotransmitter, NO, and is distributed within several caudal brainstem structures. The following studies investigated whether these neuron populations express immunoreactivity for the inducible nuclear transcription factor, Fos, in response to acute glucose deprivation. Eight days after bilateral ovariectomy and subcutaneous implantation of silastic capsules containing 30 microg estradiol benzoate/ml, adult female rats were injected i.p. with the glucose antimetabolite, 2-deoxy-D-glucose (2DG; 400 mg/kg), or the vehicle, saline, and killed by transcardial perfusion 2 h later. At 150-microm intervals through the midbrain, pons, and medulla 25-microm sections were taken and processed for dual cytoplasmic NADPH-d enzyme activity and nuclear Fos immunoreactivity (Fos-ir). Although NADPH-d-positive neurons were demonstrated in several neural structures, only those in the dorsal raphe nuclei, central subnucleus of the nucleus of the solitary tract, dorsal vagal motor nucleus, lateral paragigantocellular nucleus, nucleus ambiguus, reticular parvocellular nucleus, and medullary A5 noradrenergic cells were colabeled for nuclear Fos-ir following injection of 2DG. While NADPH-d neurons in the midbrain central gray and the latero- and posterodorsal tegmental, lateral parabrachial, motor trigeminal, and gigantocellular nuclei were not immunolabeled for Fos in the 2DG-treated animals, there was a close neuroanatomical proximity between neurons capable of generating NO and others expressing Fos-ir in these sites. These data reveal that only discrete populations of NADPH-d-containing neurons in the caudal brainstem are transcriptionally activated via the Fos stimulus-transcription cascade in response to glucose substrate imbalance, and suggest that NO and/or other neurotransmitters released by these neurons may function as neurochemical mediators of glucoprivic regulatory effects within this part of the brain.

Effect of barodenervation on c-Fos expression in the medulla induced by static muscle contraction in cats.

A previous study has shown increased Fos-like immunoreactivity (FLI), a marker of neural activation, in the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) after static muscle contraction elicited by electrical stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized, baroreceptor-intact cats. Because the electrically induced static muscle contraction reflexly increased arterial blood pressure, the concomitant activation of the arterial baroreceptor reflex during static muscle contraction may have resulted in some of the FLI labeling that was observed in the medulla. The purpose of this study was to determine regions in the medulla that are activated by muscle contraction in the absence of arterial baroreceptor input. Electrical stimulation of L7 and S1 ventral roots of the spinal cord was used to elicit static muscle contraction, and FLI in the medulla was determined in barointact and barodenervated cats. In barointact contraction cats, FLI was observed in the lateral reticular nucleus (LRN), NTS, lateral tegmental field (FTL), subretrofacial nucleus (SRF), and A1 region of the medulla. In barodenervated contraction cats, FLI increased in the same regions; however, the number of FLI-labeled cells in the NTS, FTL, and A1 region was significantly less than in barointact contraction animals. No significant difference in the number of FLI-labeled cells was found in the LRN and SRF between the two groups. These results clearly demonstrate that cardiovascular regions in the medulla are activated by input from afferent activity originating in skeletal muscle independently of concomitant arterial baroreceptor reflex activation.

Effects of intracranial self-stimulation on acetylcholine efflux in rat ventral tegmental area, nucleus accumbens and medial prefrontal cortex

Effects of intracranial self-stimulation on acetylcholine efflux in rat ventral tegmental area, nucleus accumbens and medial prefrontal cortex

Anatomically specific colocalization of NADPH-diaphorase and choline acetyltransferase in the quail brainstem

On the basis of previous studies demonstrating a wide colocalization of NADPH-diaphorase (ND) and choline acetyltransferase (ChAT) in mammalian and reptilian brainstem, ND histochemistry and ChAT immunocytochemistry have been combined to study the distribution of both markers in the mesopontine region of an avian species, the Japanese quail ( Coturnix japonica). Co-existence of the two neurochemical markers is present only in part of the system, namely, in the nucleus tegmentalis pedunculo-pontinus, in the nucleus tegmentalis latero-dorsalis, in the nucleus mesencephalicus profundus, and in the nucleus reticularis paragigantocellularis. The degree of colocalization varies in these regions from about 50 to 95% of the ChAT population. However, several other nuclei in the same region display only one of the two markers. These results confirm that even if the general distribution of the ND-positive neurons is largely comparable in vertebrates, there exists species-specific differences in the extension of the system and in the degree of colocalization with other neurochemical markers.

Elicitation and reduction of fear: behavioural and neuroendocrine indices and brain induction of the immediate-early gene c- fos

The elicitation and reduction of fear were indexed with fear-potentiated startle and corticosterone release, and induction of the immediate-early gene c- fos as a marker of neural activity in male Sprague–Dawley rats. Conditioning consisted of pairing one stimulus with footshock, which was withheld when the conditioned stimulus was preceded by a different modality stimulus, the conditioned inhibitor. On the test day, approximately 60% of the rats were used for c- fos in situ hybridization, and were presented with either the conditioned stimulus alone, the conditioned inhibitor alone, a compound of the two stimuli, or no stimuli, and killed 30 min following the presentation of 10 such stimuli. The remaining rats were tested with the fear-potentiated startle paradigm. Rats displayed reliable fear-potentiated startle and corticosterone release to the conditioned stimulus, and both measures were reduced when the conditioned stimulus was preceded by the conditioned inhibitor. The ventral bed nucleus of the stria terminalis, septohypothalamic nucleus, some tegmental nuclei, and the locus coeruleus had particularly high c- fos induction in rats that received the conditioned inhibitor, providing one of the first functional indication that these nuclei might be important in behavioural or endocrine inhibition. Conditioning specific c- fos induction in the three groups that received a stimulus on the test day was observed in many hypothalamic areas, the medial geniculate body and the central gray, structures previously involved in fear and anxiety. The cingulate, infralimbic and perirhinal cortex, nucleus accumbens, lateral septum, dorsal endopiriform nucleus, and ventral tegmental area had higher c- fos induction in rats presented with the fearful conditioned stimulus, confirming previous studies. The amygdala and hippocampus of conditioned rats did not show higher c- fos induction than in rats repeatedly exposed to the context. Many regions displayed c- fos messenger RNA induction in the control condition, suggesting that processes other than fear and anxiety participate in c- fos induction.

Neurons co-localizing calretinin immunoreactivity and reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the hippocampus and dentate gyrus of the rat

Co-localization of calretinin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity was studied in the rat hippocampus and dentate gyrus. Neurons co-expressing both markers (CR/NADPH-d) were observed throughout the hippocampus and dentate gyrus. However, they were more abundant in the stratum pyramidale and radiatum of CA3, stratum pyramidale of CA1, and in the juxtagranular zone of the hilus. The NADPH-d activity appeared in 37% of the calretinin immunoreactive neurons in CA3, 42% in CA1, and 36% in the dentate gyrus, whereas calretinin immunoreactivity occurred in 41% of the NADPH-d positive neurons in the hippocampus, and 16% in the dentate gyrus. The morphology and location of the double marked cells could not be used as a characteristic of the co-localizing neurons. The heavily stained NADPH-d neurons occurring mainly in CA1 do not show calretinin immunoreactivity. NADPH-d fiber swellings could be observed in close apposition to calretinin immunoreactive neurons and dendrites, suggesting synaptic contacts. It has been reported that calretinin immunoreactivity and NADPH-d activity co-localize infrequently in other areas such as the neocortex, striatum, hypothalamus and tegmental nucleus. The relatively high proportion of double marked cells found in the hippocampus and dentate gyrus could be indicative of the importance of the CR/NADPH-d interneurons in the circuitries of these areas.

Prenatal alcohol treatment attenuated postnatal cocaine-induced elevation of dopamine concentration in nucleus accumbens: A preliminary study

Prenatal alcohol exposure has been shown to damage the developing central nervous system (CNS) in a variety of ways, including neuroanatomical anomalies, neurochemical imbalance, and neuropharmacological dysfunction. The present study investigated one of the functional aspects of dopaminergic system in neonatal rats exposed prenatally to a binge-like alcohol paradigm by measuring dopamine concentrations following a single postnatal cocaine challenge. Pregnant Sprague-Dawley rats were given daily intragastric intubations of 5.1 g/kg alcohol solution from embryonic day (E) 1 to 20. Pair-fed and ad lib-fed animals served as controls. On E33 (usually postnatal day 10), offspring from all groups were given injections (IP) of either 0, 20, or 40 mg/kg cocaine. Animals were sacrificed and the substantia nigra/ventral tegmental area (SN/VTA) and nucleus accumbens (NAc) were dissected for the determination of dopamine concentrations using HPLC. Basal dopamine levels (0 mg/kg cocaine group) did not alter as a function of prenatal alcohol treatment in either region. However, acute cocaine injection increased the dopamine content in NAc, but not in SN/VTA, in ad lib-fed animals, and this elevation in dopamine level was significantly attenuated by prenatal alcohol treatment in both female and male animals, and by prenatal pair-fed treatment in male animals. Taken together, these results indicate that there appears to be a regional difference in acute cocaine-induced dopamine elevation, and prenatal binge-like alcohol exposure significantly alters the functional responsiveness of dopaminergic system in NAc. Furthermore, these data suggest that male offspring may be more sensitive to stress-associated or nutritional influences during gestation.

C-Fos expression in the medulla induced by static muscle contraction in cats.

In this study, we examined Fos-like immunoreactivity (FLI) in the medulla after static muscle contraction induced by stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized cats. The results show that FLI increases in the lateral reticular nucleus, nucleus of the solitary tract, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, and A1 region of the medulla in comparison with these same areas in sham-operated animals (P < 0.05 in each region). In the rostral ventrolateral medulla, FLI distribution in neurons containing phenylethanolamine-N-methyltransferase (PNMT, the synthetic enzyme for epinephrine) was also observed utilizing double-labeling methods. The majority of neurons with PNMT also expressed FLI (66 +/- 4%). These data are in contrast to the results from sham-operated animals showing that 24 +/- 3% of the neurons costained with PNMT (P < 0.05). Our findings indicate that expression of FLI can be used to identify neurons activated during static muscle contraction and support previous studies implicating the ventrolateral medulla as a critical region for expression of the exercise pressor reflex. Furthermore, neurons in the rostral ventrolateral medulla containing PNMT were activated during static muscle contraction.

Pontine acetylcholine release is regulated by muscarinic autoreceptors.

Acetylcholine (ACh) in the medial pontine reticular formation (mPRF) originates from the laterodorsal and pedunculopontine tegmental (LDT/PPT) nuclei and contributes to generating rapid eye movement (REM) sleep. The mechanisms controlling mPRF ACh levels are incompletely understood. This study tested the hypothesis that mPRF ACh release is regulated, in part, by muscarinic autoreceptors. The mPRF of intact, halothane-anesthetized cats was dialyzed with Ringer's solution (control) or Ringer's containing the muscarinic antagonist scopolamine, Scopolamine caused a dose-dependent increase in mPRF ACh release and a concomitant decrease in the number of halothane-induced cortical EEG spindles. These data suggest that presynaptic muscarinic receptors, presumed to reside on cholinergic LDT/PPT terminals in the mPRF, play a role in regulating mPRF ACh release, REM sleep and EEG spindles.

Anuran dorsal column nucleus: organization, immunohistochemical characterization, and fiber connections in Rana perezi and Xenopus laevis.

As part of a research program on the evolution of somatosensory systems in vertebrates, the dorsal column nucleus (DCN) was studied with (immuno)histochemical and tract-tracing techniques in anurans (the large green frog, Rana perezi, and the clawed toad, Xenopus laevis). The anuran DCN contains some nicotinamide adenine dinucleotide phosphate diaphorase-positive neurons, very little calbindin D-28k, and a distinct parvalbumin-positive cell population. The anuran DCN is innervated by primary and non-primary spinal afferents, by primary afferents from cranial nerves V, VII, IX, and X, by serotonin-immunoreactive fibers, and by peptidergic fibers. Non-primary DCN afferents from the spinal cord appear to arise throughout the spinal cord, but particularly from the ipsilateral dorsal gray. The present study focused on the efferent connections of the DCN, in particular the targets of the medial lemniscus. The medial lemniscus could be traced throughout the brainstem and into the diencephalon. Along its course, the medial lemniscus gives off collaterals to various parts of the reticular formation, to the octavolateral area, and to the granular layer of the cerebellum. At mesencephalic levels, the medial lemniscus innervates the lateral part of the torus semicircularis as well as various tegmental nuclei. A striking difference between the two species studied is that while in R. perezi medial lemniscal fibers do not reach the tectum mesencephali, in X. laevis, intermediate and deep tectal layers are innervated. Beyond the midbrain, both dorsal and ventral thalamic areas are innervated by the medial lemniscus. The present study shows that the anuran "lemniscal pathway" is basically similar to that of amniotes.

Physiology of arousal: Moruzzi and Magoun's ascending reticular activating system.

T he second article in this series dramatically changed the understanding of the arousal response, sleep, and waking. Like many watershed events in the history of science, the discovery and description of the ascending reticular activating system (ARAS) came about by serendipity. Professor Moruzzi, of the University of Pisa, joined Professor Magoun at Northwestern University on a series of studies exploring the role of the reticular formation in mediating the ability of the cerebellum to inhibit motor cortex activity. Stimulation of the reticular formation in cats caused an apparent flattening of the cortical EEG that the investigators originally assumed was related to cortical inhibition. However, after they increased the gain on the amplifier, they discovered that the stimulation resulted in an elimination of high-amplitude slow waves and an emergence of fast, low-amplitude EEC activity typically seen during waking.’ They subsequently went on to describe a pathway of ascending reticular relays that activates the cortex byway of diffuse thalamic projections. This discovery led to a fundamental reconceptualization of the mechanism of arousal. Hans Berger, who was the first to describe brain electrical activity in humans, first described the breaking up of alpha activity by eye opening.2 This was thought to be related to the arousing effects of sensory afferent stimulation. Sleep was seen as a passive process that emerged when afferent sensory information was inadequate to maintain arousal.3 The discovery of the ARAS led to the concept that wakefulness was an intrinsic feature of the central nervous system and was not dependent on classical sensory inputs. Moruzzi and Magoun’s concept of the ARAS has endured remarkably intact for more than half a century. Multiple studies have validated the role of the reticular formation in mediating arousal and have demonstrated the contributions of a variety of neurotransmitters, particularly acetylcholine, dopamine, histamine, norepinephrine, and serotonin.4 Recently, Mesulam has called for an expanded concept of the ARAS to include projections from the basal forebrain and hypothalamus, ventral tegmental area, locus ceruleus, and raphe nuclei in addition to the reticulothalamic pathways.5