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

Roland, Jessica J.; Savage, Lisa M.

doi:10.1016/j.nlm.2006.07.007

Cited by 29 publications

(34 citation statements)

References 66 publications

(86 reference statements)

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“…However, there was a similar increase in striatal ACh efflux in both groups suggesting there was no striatal cholinergic dysfunction following PTD treatment. Thus, similar to the data obtained by Roland and Savage (2007) using a matching to position task, ACh functioning in the striatum appeared to be spared and functional during spontaneous alternation testing following PTD treatment. It should be noted that spontaneous alternation has been shown to rely heavily upon an intact and functional hippocampal system and that this task is sensitive to fluctuations of ACh in the hippocampus (McIntyre et al, 2002).…”

Section: Discussionsupporting

confidence: 81%

Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands

Vetreno

Anzalone

Savage

2008

Neurobiology of Learning and Memory

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Diencephalic amnesia manifests itself through a host of neurological and memory impairments. A commonly employed animal model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), results in brain lesions and impairments similar in nature and distribution to those observed in humans with Wernicke-Korsakoff syndrome (WKS). In the current investigation, 2 separate experiments were conducted in which acetylcholine (ACh) efflux was assessed in the hippocampus and striatum of PTD-treated and pair-fed (PF) control male Sprague-Dawley rats. The goal was to determine under what behavioral conditions and in which brain structures ACh efflux was spared, impaired, or adaptively enhanced. In Experiment 1, rats were assessed on a spontaneous alternation task; in Experiment 2, rats were tested on a T-maze discrimination task that could be learned via a hippocampal-or striatal-based strategy. In Experiment 1, PTD-treated rats were impaired on the spontaneous alternation task and ACh efflux in the hippocampus during testing was significantly reduced, but spared in the striatum. In Experiment 2, PTD-and PF-treated rats did not differ in the number of trials to criterion, but PTD-treated rats demonstrated greater reliance upon egocentric cues to solve the task. Furthermore, ACh efflux in the striatum was greater during maze learning in the PTD-treated animals when compared to the PF animals. These results suggest that there is behavioral and systems level plasticity that can facilitate the use of alternative strategies to solve a task following diencephalic damage and WKS.

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Section: Discussionsupporting

confidence: 81%

Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands

Vetreno

Anzalone

Savage

2008

Neurobiology of Learning and Memory

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“…The data replicate that PTD rats have impaired hippocampal ACh release that is evident only under conditions of spatial exploration or place learning [46,49]. In addition, the unbiased stereological estimate of cell counts also replicates the profile counting method of assessment of loss of ChAT immunopositive cells in the MS/DB of PTD treated rats [43,44].…”

Section: Discussionsupporting

confidence: 69%

“…Using a rodent model of WKS, pyrithiamine-induced thiamine deficiency (PTD), we have demonstrated that the hippocampus is functionally impaired: When PTD-rats are performing a spontaneous alternation task [49] or learning a nonmatching-to-position task [46] the rise in hippocampal acetylcholine (ACh) efflux is blunted relative to control rats. This impairment in hippocampal ACh efflux is only evident during behavioral testing as baseline levels of hippocampal ACh are normal in the PTD model.…”

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confidence: 99%

Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

2007

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A rodent model of diencephalic amnesia, pyrithiamine-induced thiamine deficiency (PTD), was used to investigate diencephalic-limbic interactions. In-vivo acetylcholine (ACh) efflux, a marker of memory-related activation, was measured in the hippocampus and the amygdala of PTD-treated and pair-fed (PF) control rats while they were tested on a spontaneous alternation task. During behavioral testing, all animals displayed increases in ACh efflux in both the hippocampus and amygdala. However, during spontaneous alternation testing ACh efflux in the hippocampus and the alternation scores were higher in PF rats relative to PTD-treated rats. In contrast, ACh efflux in the amygdala was not suppressed in PTD treated rats, relative to PF rats, prior to or during behavioral testing. In addition, unbiased stereological estimates of the number of choline acetyltransferase (ChAT) immunopositive neurons in the medial septal/diagonal band (MS/DB) and nucleus basalis of Meynert (NBM) also reveal a selective cholinergic dysfunction: In PTD-treated rats a significant loss of ChAT-immunopositive cells was found only in the MS/DB, but not in the NBM. Significantly, these results demonstrate that thiamine deficiency causes selective cholinergic dysfunction in the septohippocampal pathway. Keywords diencephalon; hippocampus; amygdala; microdialysis; acetylcholine; stereology Selective septohippocampal-but not forebrain amygdalarcholinergic dysfunction in diencephalic amnesiaDiencephalic lesions are seen in a range of disorders: malnourishment, ischemic infarcts, viral infections, tumors and traumatic damage. Damage to certain nuclei and fiber systems within the diencephalon interrupts the flow of information between key memory structures and thus causes severe and long-lasting amnesia [25,29,45]. Although there is evidence that lesions to particular diencephalic nuclei result in memory impairment in their own right, there is also evidence that damage to diencephalic nuclei can disrupt memory circuits leading to dysfunction in other regions of the brain [4,29,45,49,53].Corresponding author: Lisa M. Savage, Department of Psychology, Binghamton University, State University of New York, Binghamton, NY, 13902, e-mail: lsavage@binghamton.edu, fax: 607-777-4890. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. At one point, WKS patients were labeled as "temporal lobe-related amnesiacs" based on their memory performance [10]. This clinical population was critical for the development of the memory system classifications (i.e., declarative vs. nondeclarative memory [51]). However, it is clear from...

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“…In recent years, some microdialysis studies have also examined the role of acetylcholine (ACh) release on learning and memory components during maze task performance (e.g. Pych et al, 2005;Roland and Savage, 2007). However, the poor temporal resolution of microdialysis sampling technique gives challenges to detect rapid biological processes in the brain during memory task performance.…”

Section: Introductionmentioning

confidence: 99%

A novel delayed non-match to sample object recognition task that allows simultaneous in vivo microdialysis

Ihalainen

Sarajärvi²,

Kemppainen

et al. 2010

Journal of Neuroscience Methods

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

Cited by 29 publications

References 66 publications

Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands

Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands

Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

A novel delayed non-match to sample object recognition task that allows simultaneous in vivo microdialysis

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