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

Savage, Lisa M.; Roland, Jessica J.; Klintsova, Anna Y.

doi:10.1016/j.brainres.2006.12.083

Cited by 30 publications

(54 citation statements)

References 58 publications

(129 reference statements)

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“…Stereological estimates of the total number of ChAT+ neurons within the of MS/DB replicated previous findings that PTD treatment reduces (≈25%) the number of ChAT+ neurons that reside within the MS/DB (Roland and Savage, 2009; Savage et al, 2007), compared to PF control (F[1, 56]=18.42, p<0.01). A novel finding was that exercise (F[1, 56]=4.64, p<0.05) led to an increase in the number of cells that expressed the ChAT+ phenotype in the MS/DB (Figure 7, Panels A–B).…”

Section: Resultssupporting

confidence: 79%

“…The parameters employed were based on previously published studies (Li et al, 2008; Roland and Savage, 2009; Savage et al, 2007; Yoder and Pang, 2005). An experimenter blind to both the Treatment, Exercise and Time point conditions performed cell counts.…”

Section: Methodsmentioning

confidence: 99%

“…We employed the pyrithiamine-induced thiamine deficiency (PTD) rat model of the amnestic disorder KS because of its high face and construct validity in replicating neuropathology and behavioral impairment (Savage et al, 2012). Although the hallmark neuropathology in both the PTD model, and KS, is neuronal loss in the anterior and midline thalamus as well as the mammillary bodies, there is a significant loss (30–40%) loss of MS/DB cholinergic neurons with concomitant reductions in cholinergic innervation of the hippocampus that leads to blunted hippocampal behaviorally-stimulated ACh efflux (Anzalone et al, 2010; Savage et al, 2007; Schliebs and Arendt, 2011). Furthermore, the PTD model is responsive to cholinergic modulation: increasing cholinergic tone within the septohippocampal circuit reduces or eliminates the amnestic profile of the PTD model (Roland et al, 2010; Roland et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior

Hall

Savage

2016

Experimental Neurology

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Exercise has been shown to improve cognitive functioning in a range of species, presumably through an increase in neurotrophins throughout the brain, but in particular the hippocampus. The current study assessed the ability of exercise to restore septohippocampal cholinergic functioning in the pyrithiamine-induced thiamine deficiency (PTD) rat model of the amnestic disorder Korsakoff Syndrome. After voluntary wheel running or sedentary control conditions (stationary wheel attached to the home cage), PTD and control rats were behaviorally tested with concurrent in vivo microdialysis, at one of two time points: 24-hrs or 2-wks post-exercise. It was found that only after the 2-wk adaption period did exercise lead to an interrelated sequence of events in PTD rats that included: (1) restored spatial working memory; (2) rescued behaviorally-stimulated hippocampal acetylcholine efflux; and (3) within the medial septum/diagonal band, the reemergence of the cholinergic (choline acetyltransferase [ChAT+]) phenotype, with the greatest change occurring in the ChAT+/nestin+ neurons. Furthermore, in control rats, exercise followed by a 2-wk adaption period improved hippocampal acetylcholine efflux and increased the number of neurons co-expressing the ChAT and nestin phenotype. These findings demonstrate a novel mechanism by which exercise can modulate the mature cholinergic/nestin neuronal phenotype leading to improved neurotransmitter function as well as enhanced learning and memory.

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Section: Resultssupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior

Hall

Savage

2016

Experimental Neurology

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“…Using the pyrithiamine-induced thiamine deficiency (PTD) animal model of WKS, our laboratory has demonstrated a functional impairment of the hippocampus as evidenced by blunted hippocampal acetylcholine (ACh) efflux when rats were tested on spontaneous alternation (Savage et al, 2003;Savage, Roland, & Klintsova, 2007) and nonmatching-toposition tasks . The observed deficits in behavior and hippocampal ACh efflux could be the result of a number of several factors.…”

Section: Introductionmentioning

confidence: 99%

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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“…Morphological studies have demonstrated that LS-hippocampus-hypothalamus-midbrain consisted limbic midbrain loop is an important pathway to hippocampus and act on regulating excitability of hippocampal neurons (Kendig et al, 1991;Franks and Lieb, 1994), and septohippocampal pathway has connection with anesthesia and amnesia (Savage et al, 2007). In our study, we observed that Fos expression was detected in the LS, CA1, DG, DM, Cg1, Cg2, PAG, and PV under incomplete anesthesia induced by sevoflurane, and more regions were detected under complete anesthesia.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Sevoflurane Inhalation on Gabaergic Neurons Activation: Observation on the GAD67‐GFP Knock‐In Mouse

Han

Zhang

Wang

et al. 2010

The Anatomical Record

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The mechanisms underlying volatile anesthesia agents are not well elucidated. Emerging researches have focused on the participation of c-aminobutyric acid (GABA) neurons but there still lacks morphological evidence. To elucidate the possible activation of GABAergic neurons by sevoflurane inhalation in morphology, Fos (as neuronal activity marker) and GABA neurons double labeling were observed on the brain of glutamic acid decarboxylase (GAD) 67-GFP knock-in mice after sevoflurane inhalation. Twenty GAD67-GFP knock-in mice were divided into three groups: S1 group: incomplete anesthesia state induced by sevoflurane; S2 group: complete anesthesia state induced by sevoflurane; control(C) group. Sevoflurane induced a significant increase of Fos expression in the dorsomedial hypothalamic nucleus (DM), periaqueductal grey (PAG), hippocampus (CA1, DG), paraventricular thalamic nucleus (PV), lateral septal nucleus (LS), and cingulate cortex (Cg1 and Cg2) in S1 group compared to C group, and increase of Fos expression in S2 group compared to S1 group. In S2 group, Fos was only expressed in the medial amygdaloid nucleus (MeA), Edinger-Westphal (E-W) nucleus, arcuate hypothalamic nucleus (Arc) and the ventral part of paraventricular hypothalamic nucleus (PaV). Double immunofluroscent staining indicated that in LS, almost all Fos were present in GABAergic neurons. In CA1, DG, DM, cg1, cg2, and PAG, Fos was expressed as well, but only few were present in GABAergic neurons. Fos expression was very high in thalamus, but no coexistence were found as no GABAergic neuron was detected in this area. Our results provided morphological evidence that GABAergic transmission in specific brain areas may participate in the sevoflurane-induced anesthesia. Anat Rec, 293:2114Rec, 293: -2122

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

Cited by 30 publications

References 58 publications

Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior

Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior

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

The Effect of Sevoflurane Inhalation on Gabaergic Neurons Activation: Observation on the GAD67‐GFP Knock‐In Mouse

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