Effects of intralaminar thalamic lesions on sensory attention and motor intention in the rat: a comparison with lesions involving frontal cortex and hippocampus

Burk, Joshua A.; Mair, Robert G.

doi:10.1016/s0166-4328(01)00202-9

Cited by 62 publications

(61 citation statements)

References 59 publications

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“…The measured increases in intentional exploratory behavior seen in the stimulated rats can be compared with studies that demonstrate deficits in initiating motor behaviors after CL lesions (31). Importantly, the effects demonstrated above are rewardindependent, indicating that CL stimulation can influence behavior without the use external incentives consistent with a generalized arousal effect producing increase behavioral responsiveness (19,32).…”

Section: Discussionmentioning

confidence: 94%

Cognitive enhancement with central thalamic electrical stimulation

Shirvalkar¹,

Seth²,

Schiff

et al. 2006

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

131

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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: Discussionmentioning

confidence: 94%

Cognitive enhancement with central thalamic electrical stimulation

Shirvalkar¹,

Seth²,

Schiff

et al. 2006

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

131

View full text Add to dashboard Cite

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“…The intralaminar thalamic nuclei have eVerent and afferent connections with the striatum; these connections have been shown to be important in the control of arousal and attention (Mair, Koch, Newman, Howard, & Burk, 2002). Lesions of the IML have been shown to affect striatal-dependent tasks such as the serial reaction time (SRT) task (Burk & Mair, 2001). The SRT task involves the performing of "habitlike" behavioral responses to exterior stimuli.…”

Section: Discussionmentioning

confidence: 99%

Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

Roland

Savage

2007

Neurobiology of Learning and Memory

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A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate the dynamic role of hippocampal and striatal acetylcholine (ACh) efflux across acquisition of a nonmatching-to-position (NMTP) T-maze task. Changes in ACh efflux were measured in rats at different time points in the acquisition curve of the task (early= day 1, middle = day 5, and late = day 10). Overall, the control group had higher accuracy scores than the PTD group in the latter sessions of NMTP training. During the three microdialysis sampling points, all animals displayed significant increases in ACh efflux in both hippocampus and striatum, while performing the task. However, on day 10, the PTD group showed a significant behavioral impairment that paralleled their blunted hippocampal-but not striatal-ACh efflux during maze training. The results support selective diencephalic-hippocampal dysfunction in the PTD model. This diencephalichippocampal interaction appears to be critical for successful episodic and spatial learning/memory.

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“…Although one study reported persistent reductions in accuracy on the 5CSRT test following lesions to the temporal hippocampus (made before pretraining), these were accompanied by large increases in perseverative responding, with the number of premature responses not reported (Le Pen et al 2003). Consistent with hippocampal lesions disrupting aspects of inhibitory response control required on the 5CSRT test, rather than sustained attention, complete hippocampal lesions did not affect attentional performance on a prefrontal-dependent self-paced serial-reaction task requiring little impulse control (Burk and Mair 2001). In contrast, sustained attention is highly dependent on balanced prefrontal activity, with prefrontal lesions (Chudasama and Robbins 2006), functional inhibition (by the GABA-A agonist muscimol) or disinhibition ) all markedly disrupting attention on the 5CSRT test.…”

Section: Attentional Deficitsmentioning

confidence: 95%