Generalized arousal of mammalian central nervous system

Pfaff, Donald W.; Westberg, Lars; Kow, Lee‐Ming

doi:10.1002/cne.20720

Cited by 33 publications

(13 citation statements)

References 75 publications

(59 reference statements)

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“…Exploratory activity relevant to the goal (measured in seconds as time spent with both the novel and the old object) significantly increased in stimulated animals (P Ͻ 0.01 across days; and, 50.4 Ϯ 6.8 vs. 33.9 Ϯ 3.0, P Ͻ 0.05, stimulated versus control within day 3) across 3 days, indicating that repeated stimulation of CL specifically influences intentional activity related to task performance. The observations are consistent with previous demonstrations that increased motor activity reflects a change in generalized arousal (18). Note that stimulation did not induce seizure-like behavior (see Methods) or impairment in general motor function.…”

Section: Experiments 2: Enhancement Of Object Recognition Performance supporting

confidence: 92%

Cognitive enhancement with central thalamic electrical stimulation

Shirvalkar¹,

Seth²,

Schiff

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

134

103

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Central thalamic electrical stimulation has been proposed as a method for remediation of acquired cognitive disability. Longstanding experimental and clinical observations indicate a key role for neurons within the central thalamus in maintaining the alert waking state and facilitating attended behaviors. Here, we show that continuous high frequency (100 Hz) electrical stimulation of the central thalamus generates widespread cortical activation of c-fos across all cortical layers and a selective pattern of regulation of zif268 within the supragranular, granular, and infragranular cortical laminae. Significant elevation of both immediate early genes also is seen in the dentate gyrus of the hippocampus. Use of the same stimulation parameters is shown to facilitate untrained goal-directed seeking behavior and object recognition memory in rodents. An overall increase of exploratory motor behaviors and grooming activity also is observed, consistent with a global increase in arousal. Taken together, these studies indicate that electrical stimulation of the central thalamus may enhance cognitive performance through neocortical and hippocampal neuronal activation and specific regulation of gene expression.attention ͉ deep brain stimulation ͉ gene expression ͉ intralaminar thalamus ͉ neuromodulation E lectrical stimulation of brainstem, thalamic, and basal ganglia structures is a rapidly emerging therapeutic technique for neuropsychiatric disorders, but knowledge of underlying mechanisms is limited (1, 2). Central thalamic stimulation has been proposed for the treatment of impaired cognitive function (3). Neurons within the intralaminar nuclei and paralaminar regions of the central thalamus link brainstem arousal systems to cerebral cortical and basal ganglia networks crucial to the organization of wakeful behaviors (4-8). To investigate the impact of central thalamic electrical stimulation on cognitive function, we characterize gene expression and behavioral effects of electrical stimulation centered on the central lateral (CL) nucleus of the rat anterior intralaminar thalamic nuclei (part of the central thalamus). We hypothesize that electrical stimulation of CL and surrounding regions may increase vigilance and cognitive performance in the intact animal. We assess functional activation associated with CL stimulation by using patterns of immediate-early gene expression in cortical and subcortical structures. Electrical stimulation of CL produced ipsilateral up-regulation of c-fos and zif268 expression with laminar specificity in the motor cortex (mCtx), anterior cingulate cortex (ACC), caudate-putamen (CP), and bilateral elevation in hippocampi at 2 hours after stimulation. In a separate series of experiments, unilateral high-frequency (100 Hz) electrical stimulation of CL in awake animals produced significant improvements in performance and learning of a visual object recognition task compared with control animals. These findings indicate that in vivo stimulation of central thalamus targeting CL activates a wide cereb...

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Section: Experiments 2: Enhancement Of Object Recognition Performance supporting

confidence: 92%

Cognitive enhancement with central thalamic electrical stimulation

Shirvalkar¹,

Seth²,

Schiff

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

134

103

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“…The PVN plays an important role in arousal, autonomic, and behavioral responses to stressors (41). It has reciprocal connections with arousal centers, such as locus coeruleus and raphe nuclei (4,59).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai¹,

Kapás²,

Krueger³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

110

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Szentirmai É , Kapás L, Krueger JM. Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats. Am J Physiol Regul Integr Comp Physiol 292: R575-R585, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00448.2006.-Ghrelin, a gutbrain peptide, is best known for its role in the stimulation of feeding and growth hormone release. In the brain, orexin, neuropeptide Y (NPY), and ghrelin are parts of a food intake regulatory circuit. Orexin and NPY are also implicated in maintaining wakefulness. Previous experiments in our laboratory revealed that intracerebroventricular injections of ghrelin induce wakefulness in rats. To further elucidate the possible role of ghrelin in the regulation of arousal, we studied the effects of microinjections of ghrelin into hypothalamic sites, which are implicated in the regulation of feeding and sleep, such as the lateral hypothalamus (LH), medial preoptic area (MPA), and paraventricular nucleus (PVN) on sleep in rats. Sleep responses, motor activity, and food intake after central administration of 0.04, 0.2, or 1 g (12, 60, or 300 pmol) ghrelin were recorded. Microinjections of ghrelin into the LH had strong wakefulness-promoting effects lasting for 2 h. Wakefulness was also stimulated by ghrelin injection into the MPA and PVN; the effects were confined to the first hour after the injection. Ghrelin's non-rapid-eye-movement sleepsuppressive effect was accompanied by attenuation in the electroencephalographic (EEG) slow-wave activity and changes in the EEG power spectrum. Food consumption was significantly stimulated after microinjections of ghrelin into each hypothalamic site. Together, these results are consistent with the hypothesis that forebrain ghrelinergic mechanisms play a role in the regulation of vigilance, possibly through activating the components of the food intake-and arousalpromoting network formed by orexin and NPY. lateral hypothalamus; medial preoptic area; paraventricular nucleus; electroencephalogram; slow-wave activity; sleep GHRELIN IS A 28-AMINO ACID peptide produced by endocrine cells in the gastrointestinal system and by neurons in the central nervous system (21). Circulating ghrelin is derived mainly from the stomach (1). Plasma ghrelin levels inversely correlate with feeding; fasting increases, while food intake reduces, plasma ghrelin concentrations (7, 61). In the brain, ghrelin is produced by arcuate nucleus (ARC) neurons and by a distinct hypothalamic neuronal population in the internuclear region (6). Ghrelin's actions are mediated by the growth hormone secretagogue receptor (GHS-R) (21). GHS-R mRNA is widely distributed in the gastrointestinal tract, sensory vagus fibers, and the brain. Those hypothalamic nuclei that are implicated in the regulation of feeding and/or sleep-wake activity, such as the lateral hypothalamus (LH), paraventricular nucleus (PVN), ARC, dorsomedial hypothalamic nucleus, anteroventral preoptic nucleus, anterior hypothalamic area, suprachiasmatic nucleus, anterolateral hypothalamic nucleus, and the...

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“…This phase is realized through bidirectional connections among amygdala, hypothalamus, and the brain stem (cf. Pfaff, et al, 2005). In his neurobiological model of emotion regulation Lewis (2005) emphasized multiple positive and negative feedback components originating from brain stem which back up to amygdala and other cortical and subcortical systems increasing the activation of some systems while decreasing it in others.…”

Section: Putative Scenario Of Neural Computations During the Scr Processmentioning

confidence: 99%

Assessment of Brain Monoaminergic Signaling Through Mathematical Modeling of Skin Conductance Response

Branković¹

2012

Neuroscience - Dealing With Frontiers

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Generalized arousal of mammalian central nervous system

Cited by 33 publications

References 75 publications

Cognitive enhancement with central thalamic electrical stimulation

Cognitive enhancement with central thalamic electrical stimulation

Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Assessment of Brain Monoaminergic Signaling Through Mathematical Modeling of Skin Conductance Response

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