Biomedical subjects

Barry D Waterhouse

Publications and source records attributed to Barry D Waterhouse.

At least 19 recordsLinked to original sources

PubMed2006

Locus ceruleus regulates sensory encoding by neurons and networks in waking animals.

Substantial evidence indicates that the locus ceruleus (LC)-norepinephrine (NE) projection system regulates behavioral state and state-dependent processing of sensory information. Tonic LC discharge (0.1-5.0 Hz) is correlated with levels of arousal and demonstrates an optimal firing rate during good performance in a sustained attention task. In addition, studies have shown that locally applied NE or LC stimulation can modulate the responsiveness of neurons, including those in the thalamus, to nonmonoaminergic synaptic inputs. Many recent investigations further indicate that within sensory relay circuits of the thalamus both general and specific features of sensory information are represented within the collective firing patterns of like-modality neurons. However, no studies have examined the impact of NE or LC output on the discharge properties of ensembles of functionally related cells in intact, conscious animals. Here, we provide evidence linking LC neuronal discharge and NE efflux with LC-mediated modulation of single-neuron and neuronal ensemble representations of sensory stimuli in the ventral posteriomedial thalamus of waking rats. As such, the current study provides evidence that output from the LC across a physiologic range modulates single thalamic neuron responsiveness to synaptic input and representation of sensory information across ensembles of thalamic neurons in a manner that is consistent with the well documented actions of LC output on cognition.

Animals↗

PubMed2006

Acute restraint increases NADPH-diaphorase staining in distinct subregions of the rat dorsal raphe nucleus: implications for raphe serotonergic and nitrergic transmission.

The brainstem dorsal raphe nucleus (DRN) maintains a rough topographic cell ordering with respect to biological function. This study examined the influence of acute restraint on nitric oxide (NO) synthase (NOS) neurons in distinct DRN subregions. NADPH diaphorase staining (NOS index) intensity was higher in the DRN dorsomedial, ventromedial and lateral wings subregions of restrained vs. control rats. The mean number of cells was not significantly different between both groups of animals. The restrained-induced NADPH-diaphorase activity was significantly higher in the rostral ventromedial and caudal lateral wings than the corresponding caudal and rostral subregions but no significant difference was observed between rostral and caudal dorsomedial subregions. These observations suggest that restraint stress differentially activates NO-producing neurons in distinct DRN subregions.

Acute Disease↗

PubMed2006

Acute capsaicin injection increases nicotinamide adenine dinucleotide phosphate diaphorase staining independent of Fos activation in the rat dorsolateral periaqueductal gray.

The mesencephalic dorsolateral periaqueductal gray (dlPAG) mediates different modalities of aversive behaviors including pain and nociception and is anatomically delineated from other columns of the PAG by its content of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). In many brain regions, neuronal NADPH-d is a nitric oxide (NO) synthase (NOS) and NO production mediates many nociceptive and aversive behavioral responses. The aim of this study was to determine how the noxious stimulant capsaicin affects intracellular dynamics in the dlPAG evidenced by Fos protein immunoreactivity (index of intracellular activation) and the NADPH-d reactivity. The basic hypothesis tested was that the effect of systemic capsaicin administration involved activation of the NO-producing machinery in the dlPAG. Compared to vehicle, capsaicin (50mg/kg, subcutaneous) significantly increased NADPH-d reactivity and Fos expression along the dlPAG neuraxis. However, less than one percent of the capsaicin-induced Fos activation occurred in NADPH-d-positive cells. This suggests that different intracellular mechanisms involving NO and activation of at least one other transmitter substance underlie the effects of capsaicin in the dlPAG. Although NADPH-d is a marker for constitutive NOS, only about two-thirds of the NADPH-d-positive neurons in the dlPAG were colocalized with neuronal NOS immunoreactive cells. This observation suggests that in contrast to other brain regions, neuronal NOS is unlikely to account for all NADPH-d activity in the dlPAG. Taken together, the present results show that the effect of capsaicin requires activation of at least one other transmitter and NADPH-d-dependent NO synthesis involving, but not limited to, the neuronal NOS isoform.

Animals↗

PubMed2006

Activity-dependent heterogeneous populations of nitric oxide synthase neurons in the rat dorsal raphe nucleus.

The brainstem dorsal raphe nucleus (DRN) contains an abundant distribution of nitric oxide (NO) synthase (NOS)-containing neuronal profiles in two distinct populations: faint- and intense-immunoreactive cells in midline (ventromedial and dorsomedial) and lateral wing subregions, respectively. This study tested the hypothesis that different functional dynamics underlie the topography of NOS-containing cells in the DRN rostrocaudal and mediolateral neuraxis by using a capsaicin challenge paradigm (50 mg/kg, subcutaneous). Compared with vehicle, capsaicin significantly and preferentially increased nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d, an index of constitutive NOS) reactivity in the rostral midline and caudal lateral wing subregions. Furthermore, capsaicin activated more Fos-positive cells than vehicle within all subregions of the DRN but with a caudal versus rostral predominance in activation pattern. In addition, a high proportion of capsaicin-induced Fos cells in the midline but almost none in lateral wing stained for NADPH-d. These observations suggest the existence of two functionally distinct populations of NOS neurons in the DRN. Furthermore, capsaicin increased galanin immunoreactivity with predominant staining in cell soma and fiber processes in midline and lateral wing subregions of the nucleus, respectively. The total capsaicin-induced galanin immunoreactivity was higher in rostral versus caudal DRN, and a high proportion of galanin-positive cells in the midline also contained NADPH-d and neuronal NOS, thus suggesting a potential NO-galanin interaction in these neurons. The differential pattern of Fos/NADPH-d colocalization across the nucleus suggests that midline and lateral wing NOS neurons of the DRN express their neuromodulatory actions on discrete efferent targets via different intracellular mechanisms.

Analysis of Variance↗

PubMed2006

Characterization of neurochemically specific projections from the locus coeruleus with respect to somatosensory-related barrels.

Tactile information from the rodent mystacial vibrissae is relayed through the ascending trigeminal somatosensory system. At each level of this pathway, the whiskers are represented by a unique pattern of dense cell aggregates, which in layer IV of cortex are known as "barrels." Afferent inputs from the dorsal thalamus have been demonstrated repeatedly to correspond rather precisely with this modular organization. However, axonal innervation patterns from other brain regions such as the noradrenergic locus coeruleus are less clear. A previous report has suggested that norepinephrine-containing fibers are concentrated in the center/hollow of the barrel, while other studies have emphasized a more random distribution of monoaminergic projections. To address this issue more directly, individual tissue sections were histochemically processed for cytochrome oxidase in combination with dopamine-beta-hydroxylase, the synthesizing enzyme for norepinephrine, or the neuropeptide galanin. These two neuroactive agents were of particular interest because they colocalize in a majority of locus coeruleus neurons and terminals. Our data indicate that discrete concentrations or local arrays of dopamine-beta-hydroxylase- or galanin-immunoreactive fibers are not apparent within the cores of individual barrels. As such, the data suggest that cortical inputs from the locus coeruleus are not patterned according to cytoarchitectural landmarks or the neurochemical identity of coeruleocortical efferents. While transmitter-specific actions of norepinephrine and/or galanin may not be derived from the laminar/spatial connections of locus coeruleus axons, the possibility remains that the release of these substances may mediate distinctive events through the localization of different receptor subclasses, or the contact of their terminals onto cells with certain morphological characteristics or ultrastructural components.

Animals↗

PubMed2005

Retrograde study of hypocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat.

A retrograde tracer, WGA-apo-HRP-gold (WG), was injected into each subdivision of the dorsal raphe (DR) nucleus, and subsequent orexin-A immunostaining was performed for the tuberal region of the hypothalamus in order to investigate orexin projections to the DR. Similar to previous studies, the majority of orexin-single-labeled neurons were observed at the dorsal half of the lateral hypothalamus (LH), the circle around the fornix, i.e., perifornical nucleus (PeF), and the area dorsal to the fornix. The present study reports that hypothalamic neurons exhibited differential projections to each subdivision of the DR. Following WG injections into rostral DR, WG-single-labeled cells were observed at the dorsal half of the LH as well as dorsomedial hypothalamic nucleus. The major input to the intermediate DR originates from the ventromedial portion of the LH, PeF, and the area dorsal to the PeF, whereas one to lateral wing DR derived from PeF as well as the ventrolateral portion of the LH. Following WG injections into caudal DR, WG-single-labeled cells were located at ventromedial LH and the ventrolateral portion of the posterior hypothalamus. Following WG injections into each DR subdivision, WG/orexin-double-labeled neurons were observed at LH, PeF, and the area dorsal to the PeF. Only a few double-labeled cells were observed in dorsomedial and posterior hypothalamic nuclei. Our observations suggest that various hypothalamic neurons differentially project to each subdivision of the DR, a portion of which is orexin-immunoreactive. These orexin-immunoreactive DR-projecting hypothalamic neurons might have wake-related influences over a variety of brain functions subject to DR efferent regulation, including affective behavior, autonomic control, nociception, cognition, and sensorimotor integration.

Animals↗

PubMed2005

Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat.

In the first series of experiments, a retrograde tracer, WGA-apo-HRP-gold (WG), was injected into the dorsal raphe (DR) or the locus coeruleus (LC) and adenosine deaminase immunostaining was subsequently performed for the tuberomammillary nucleus (TMN) in order to investigate projections from the TMN to the two brainstem monoaminergic nuclei. Following rostral DR injections, the majority of retrogradely labeled cells were located in the dorsomedial and ventrolateral subdivisions of the TMN. At middle DR levels, midline injections resulted in labeling mainly in the ventrolateral subdivision, whereas lateral wing injections produced labeling mostly in ventral and caudal TMN subdivisions. When injections were made in the caudal DR, only a few cells were observed along the rostro-caudal extent of the TMN. On the other hand, following rostral LC injections, labeled neurons were observed mainly in ventrolateral and ventral subdivisions of TMN. For principal LC injections, labeled cells were observed mostly in ventrolateral, ventral, and caudal TMN subdivisions, whereas for injections at caudal pole of LC, only a few cells were located along the rostro-caudal extent of the TMN. In the second series of experiments, an iontophoretic injection of fluorogold (FG) into the DR was paired with a pressure injection of WG into the LC to investigate the collateral distribution of TMN axonal fibers to DR and LC. Double-labeled cells were observed in ventrolateral, ventral, and caudal TMN subdivisions. The present study indicated that there exists a robust projection from the TMN to the DR or the LC and that some TMN neurons have axon collaterals projecting to both DR and LC. The TMN neurons with such axon collaterals might provide simultaneous, possibly more efficient, way of controlling the brainstem monoaminergic nuclei, thus influencing various sleep and arousal states of the animal.

Animals↗

PubMed2005

Retrograde double-labeling study of common afferent projections to the dorsal raphe and the nuclear core of the locus coeruleus in the rat.

Common afferent projections to the dorsal raphe (DR) and locus coeruleus (LC) nuclei were analyzed in the rat by making paired injections of retrograde tracers, gold-conjugated and inactivated wheatgerm agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) and Fluorogold (FG), into the DR and the nuclear core of the LC. Our results demonstrate that the largest number of double-labeled neurons was located at various preoptic regions including medial preoptic area, lateral preoptic nucleus, and ventrolateral preoptic nucleus. The majority of labeled cells were also observed at the lateral hypothalamus, where the number of labeled cells was comparable to that of neurons at the medial preoptic area or lateral preoptic nucleus. A few double-labeled cells were observed at various hypothalamic regions including anterior, medial tuberal, posterior, and arcuate nuclei, as well as mesencephalic areas including substantia nigra compacta and ventrolateral/lateral periaqueductal gray matter. Cells were also observed at prelimbic/infralimbic prefrontal cortices, diagonal band of Broca, bed nucleus of stria terminalis, and pontine/medullary regions including various raphe nuclei, Barrington's nucleus, gigantocellularis, paragigantocellularis, prepositus hypoglossi, subcoeruleus, and dorsomedial tegmental area. Although electrophysiological studies need to be performed, a large number of double-labeled neurons located at preoptic regions as well as lateral hypothalamus might have their major role in simultaneous control over these monoaminergic nuclei as a means of influencing various sleep and arousal states of the animal. Double-labeled cells at the other locations might be positioned to influence a variety of other functions such as analgesia, cognition, and stress responses.

Afferent Pathways↗

PubMed2005

Effects of systemically administered cocaine on sensory responses to peri-threshold vibrissae stimulation: individual cells, ensemble activity, and animal behaviour.

Previous studies have shown that systemic administration of cocaine transiently alters stimulus-evoked responses of ventral posteromedial (VPM) thalamic neurons. Results from these single-unit electrophysiological studies revealed that cocaine was equally likely to augment or attenuate the magnitude of sensory evoked responses following threshold level stimulation of peripheral receptive fields. In an attempt to clarify the impact of cocaine administration on sensory signal processing, we examined the drug's effects on responses of individual neurons and ensembles of VPM thalamic neurons to sensory stimuli, and performance of subjects in a sensory detection behavioural task. Extracellular responses of single (n = 1 cell/rat) or multiple VPM thalamic neurons (n = 10-40 cells/rat) were monitored before and after cumulative doses of cocaine (0.25-2.0 mg/kg i.v.). Neuronal responses were characterized by assessing the response profile to a range of peri-threshold-level deflections of the optimal whisker on the contralateral face. Drug effects on stimulus-response curves, determined from quantitative analysis of spike train data, indicated that whereas cocaine elicits variable effects at the single cell level, the stimulus-evoked response of the recorded population was likely to increase following lower (0.25-1.0 mg/kg i.v.) doses of cocaine. Furthermore, cocaine preferentially enhanced responses to smaller magnitude deflections of vibrissa, altering the response profile from a mode that accurately conveyed stimulus strength to one that increased detection at the expense of discrimination. Finally, a similar pattern emerged in a behavioural paradigm involving rats trained to detect variable amplitude whisker pad stimulation, suggesting a common action of cocaine that may contribute to the drug's addictive properties.

Action Potentials↗

PubMed2004

The effects of tonic locus ceruleus output on sensory-evoked responses of ventral posterior medial thalamic and barrel field cortical neurons in the awake rat.

In mammals, the pontine nucleus locus ceruleus (LC) is the sole source of norepinephrine (NE) projections to the forebrain. Increasing tonic discharge of LC neurons elevates extracellular levels of NE in the cortex and thalamus. Tonic LC discharge is linked to the level of wakefulness and behavioral performance, demonstrating an optimal firing rate during sustained attention tasks. Iontophoretic application of NE to target neurons in the forebrain has been shown to produce a diverse set of neuromodulatory actions, including augmentation of synaptically evoked discharge as well as suppression of spontaneous and stimulus-evoked firing patterns. Iontophoretic studies cataloged potential NE effects; however, the context in which such actions could occur in awake behaving animals remained controversial. To address this issue, the current study examined the effects of increasing tonic LC output on spontaneous and stimulus-evoked discharge of neurons within the ventroposterior medial (VPM) thalamus and barrel field (BF) somatosensory cortex of awake animals using multichannel extracellular recording strategies. The present findings indicate two primary outcomes that result from increasing frequencies of LC stimulation, either an inverted-U facilitating response profile or monotonic suppression of sensory-evoked neuronal responses. Increased tonic LC output generally decreased neuronal response latency measures for both BF cortical and VPM thalamic cells. LC-mediated effects on target VPM and BF cortical neuron sensory processing are consistent with previous demonstrations of NE modulatory actions on central neurons but indicate that such actions are cell specific. Moreover, clear differences were observed between the modulation of VPM and BF cortical cells. These data suggest that sensory signal processing is continually altered over the range of tonic LC discharge frequencies that occur in the waking animal. Such changes may account for LC-mediated shifts in sensory network performance across multiple stages of arousal and attention.

Action Potentials↗

PubMed2004

Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat.

The interconnection between two brainstem monoaminergic nuclei, the dorsal raphe (DR) and the locus coeruleus (LC), was analyzed in the rat using retrograde tracing and immunocytochemistry. Gold-conjugated and inactivated wheatgerm agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) was injected into subdivisions of the DR or rostro-caudal levels of the nuclear core of the LC, and labeled LC or DR neurons were identified by dopamine-beta-hydroxylase (DBH) or 5-hydroxytryptamine (5-HT) immunostaining, respectively. Within the LC-DR projection, the caudal principal LC projected to the caudal, ventromedial, and interfascicular DR. Mid-LC as well as caudal LC projected with an ipsilateral predominance to the lateral wing subdivision of the DR. A few rostral LC neurons projected to caudal, dorsomedial, and ventromedial DR. Within the DR-LC projection, the rostral LC received inputs mainly from the caudal, dorsomedial, and ventromedial DR. Mid-LC to caudal LC received projections from mid-DR to caudal DR, with the heaviest projection from the ipsilateral lateral wing as well as caudal DR. The DR-LC projection was substantially more robust than LC-DR and included both serotonergic and nonserotonergic components. Thus, the data demonstrate topographically ordered, reciprocal connectivity between DR and LC with particularly strong projections from DR to LC. Communication between these two brainstem monoaminergic nuclei may be critical for a variety of functions including sleep-wake regulation, vigilance, analgesia, cognition, and stress responses.

Animals↗

PubMed2004

Sensorimotor-related discharge of simultaneously recorded, single neurons in the dorsal raphe nucleus of the awake, unrestrained rat.

Multi-channel, multi-neuron recording procedures were used to monitor simultaneously the spike train activity of single neurons (n=7-16 cells/animal) in the dorsal raphe (DR) nucleus of the awake, freely moving rat. Putative serotonergic and non-serotonergic neurons were distinguished from one another on the basis of established criteria, i.e. waveform shape and duration, firing pattern and firing frequency. As a group, presumed serotonergic neurons exhibited low tonic discharge rates, depressed firing after serotonin (5HT)-1a agonist administration, and, except for the transition from sleep to waking, a general insensitivity to specific sensory or motor events. By contrast, non-serotonergic cells in midline and lateral wing sub-regions of the nucleus displayed responses to a variety of sensorimotor events including locomotion, grooming, head movement, chewing, auditory stimuli, and whisker movement (both passive and active). However, within this latter group, the sensorimotor response repertoire of individual cells was not uniform. Likewise, non-5HT cells with diverse response profiles were identified in both medial and lateral sub-regions of the nucleus. Cells categorized as non-serotonergic also had varied responses to 5HT1a agonist administration. These results emphasize the diverse input/output relationships of individual DR neurons and underscore the need for a more comprehensive analysis of such properties under waking conditions in order to obtain a better understanding of the role of the DR nucleus in brain function.

Acoustic Stimulation↗

PubMed2004

Capsaicin increases GFAP and glutamine synthetase immunoreactivity in rat arcuate nucleus and median eminence.

Antibodies to glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were used to determine the effect of s.c. capsaicin (after 75 min) on astroglial cells in the rat arcuate nucleus-median eminence (ARC-ME). Compared to vehicle, capsaicin significantly increased GFAP and GS immunoreactivity in the ARC-ME. Co-localization of GFAP and GS was observed in the ARC-ME complex. Since GS is primarily responsible for glutamate-glutamine metabolism, the increase in total immunostaining for GFAP-and GS- staining suggests a functional adjustment to cope with some of the capsaicin-induced effects. Together with the involvement of nitric oxide synthase in the ARC-ME response to capsaicin, these observations indicate activity-dependent plasticity of the neuron-glia network in response to this stressful/noxious stimulus.

Animals↗

PubMed2004

Cocaine-induced vs. behaviour-related alterations of spontaneous and evoked discharge of somatosensory cortical neurons.

While the abuse potential of cocaine stems mainly from its ability to increase dopaminergic transmission in limbic regions, drug actions on other monoamine-innervated circuits may contribute to the development and maintenance of cocaine addiction. Previous extracellular recordings in anaesthetized rats revealed a facilitatory influence of cocaine on primary sensory pathways, which could influence the processing of drug-related stimuli during the development of cocaine addiction. We further analysed these sensory effects of cocaine in freely behaving rats (n = 9). Using an array of eight microelectrodes chronically implanted in infragranular layers of primary somatosensory cortex, we recorded the basal activity of 40 single- and 64 multiunits and their response to electrical stimulation of the whisker pad before and after incremental doses of cocaine (0.25-2 mg/kg i.v.). Both spontaneous and cocaine-induced explorations were associated with elevated basal firing of the cortical neurons and suppression of their short-latency excitation and postexcitatory inhibition in response to the whisker-pad stimulation. In addition to exploration-related alterations, the administration of cocaine enhanced the long-latency rebound excitation induced by the whisker-pad stimulation. This component of the sensory response, which is more labile and does not seem to convey information about the physical characteristics of the stimulus, may participate in the processing of drug-related sensory stimuli.

Action Potentials↗

PubMed2003

Differential expression of nitric oxide in serotonergic projection neurons: neurochemical identification of dorsal raphe inputs to rodent trigeminal somatosensory targets.

The dorsal raphe (DR) is invested with nitric oxide synthase (NOS)-expressing profiles. To characterize the connections of NO-containing cells and further assess neurochemical relationships maintained by DR, the transmitter identity of the raphe projection to the trigeminal somatosensory system was examined. Rats were injected with retrograde tracer into vibrissae-related target areas or with anterograde tracer into DR. NADPH-diaphorase (NADPHd) histochemistry or NOS-immunostaining was combined with serotonin (5HT)- or serotonin transporter (SERT)-immunolabeling to examine: 1) the presence of NO in 5HT-containing axons from DR; 2) the distribution of NO-containing fibers with respect to other nitrergic profiles in the somatosensory system; and 3) the propensity for individual projection neurons in specific subdivisions of DR to colocalize 5HT and NO. Results confirm that "barrel-like" patches can be identified in several adult trigeminal relay nuclei by NADPHd histochemistry and demonstrate that fibers from DR contain 5HT and NO. Observations include a high percentage of cortical midline projection neurons which contained NADPHd (70-80%) and coexpressed 5HT. In contrast, approximately 40% of retrogradely labeled DR-thalamus cells in the lateral wing demonstrated NADPHd or 5HT expression, but not both in the same neuron. Colocalization of NADPHd and 5HT within individual DR projection neurons indicates that: i) DR is a source of nitrergic input to trigeminal structures, and ii) NO and 5HT may be simultaneously released to influence information-processing within somatosensory targets. Disparities in NADPHd expression between retrogradely labeled DR neuronal subpopulations further suggest functional differences in the impact of NO on cortical and subcortical targets.

Animals↗

PubMed2003

Inter- and intra-nuclear differences in galanin expression between the hypothalamic paraventricular and supraoptic nuclei in colchicine-untreated rats.

Not much is known of the topography of galanin expression in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei neurons in colchicine (an axoplasmic inhibitor)-untreated animals. Insight into the biological implication(s) of galanin expression in the PVN and SON will depend, at least in part, on the nature of its distribution in colchicine-untreated animals. In this study therefore, the topographical distribution of galaninergic profiles was examined in the PVN and SON of colchicine-untreated rats. Staining in the parvocellular PVN (PVN(p)) was predominantly as varicose thin galanin fiber processes while the magnocellular PVN (PVN(m)) contained large cell soma and fiber processes. The relative fiber density was higher in the anterior, periventricular and medial PVN(p) than in the dorsal, lateral and posterior subdivisions. Large-sized cells and thick fibers were limited to the posterior PVN(m) while the anterior and medial PVN(m) contained varicose profiles. Light- and intensely-stained galanin-positive cells as well as large- and small-diameter (varicose or non-varicose) fibers were observed in the SON. The large and thin fibers exhibit preferential ventral and dorsal distribution, respectively. Together with the complexity of specific afferent and efferent connections within the PVN and SON, these observations underscore heterogeneous galanin expression and raise potential implications for understanding the biological role of galanin by physiologically challenging stimuli.

Animals↗

PubMed2003

Glutamatergic afferent projections to the dorsal raphe nucleus of the rat.

Based on WGA-apo-HRP-gold (WG) retrograde tracing, the present study revealed that different subdivisions of the dorsal raphe (DR) such as dorsomedial, ventromedial, lateral wing, and caudal regions receive unique, topographically organized afferent inputs, that are more restricted than previously reported. Phaseolus vulgaris leucoagglutinin anterograde tracing studies confirmed that the medial prefrontal cortex provides the major afferent input to each subdivision of the DR. Double-labeling studies combining WG tracing and glutamate immunostaining indicated that the medial prefrontal cortex, various hypothalamic nuclei including perifornical, lateral, and arcuate nuclei, and several medullary regions such as lateral and medial parabrachial nuclei, and laterodorsal tegmental nucleus provide the major glutamatergic input to each subregion of the DR. It should be noted that the degree of glutamatergic input from these afferent sites was specific for each DR subdivision. The present findings indicated that dorsomedial, ventromedial, lateral wing, and caudal subdivisions of the DR receive excitatory inputs from both cortical and subcortical sites which might be involved in regulation or modulation of a broad range of systems, including sensory and motor functions, arousal and sleep-wake cycle, biorhythmic, cognitive, and affective behaviors.

Animals↗

PubMed2003

The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes.

Through a widespread efferent projection system, the locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. Initial studies provided critical insight into the basic organization and properties of this system. More recent work identifies a complicated array of behavioral and electrophysiological actions that have in common the facilitation of processing of relevant, or salient, information. This involves two basic levels of action. First, the system contributes to the initiation and maintenance of behavioral and forebrain neuronal activity states appropriate for the collection of sensory information (e.g. waking). Second, within the waking state, this system modulates the collection and processing of salient sensory information through a diversity of concentration-dependent actions within cortical and subcortical sensory, attention, and memory circuits. Norepinephrine-dependent modulation of long-term alterations in synaptic strength, gene transcription and other processes suggest a potentially critical role of this neurotransmitter system in experience-dependent alterations in neural function and behavior. The ability of a given stimulus to increase locus coeruleus discharge activity appears independent of affective valence (appetitive vs. aversive). Combined, these observations suggest that the locus coeruleus-noradrenergic system is a critical component of the neural architecture supporting interaction with, and navigation through, a complex world. These observations further suggest that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective disorders, including post-traumatic stress disorder. Independent of an etiological role in these disorders, the locus coeruleus-noradrenergic system represents an appropriate target for pharmacological treatment of specific attention, memory and/or arousal dysfunction associated with a variety of behavioral/cognitive disorders.

Adrenergic Uptake Inhibitors↗