Intraseptal infusion of oxotremorine impairs memory in a delayed-non-match-to-sample radial maze task
Section snippets
Subjects
Twenty-four, male Sprague–Dawley (Charles Rivers, MA, USA) rats were housed individually in Plexiglas pens. Rats were approximately 1.5 months old at the start of the training. The animal room was maintained between 72 and 74 °F on a 12-h light/dark cycle (lights on at 7 AM). Water was available ad libitum. Beginning with the habituation trials, rats were food-deprived to 80–85% of their free-feeding weight. Following this period, the rats were weighed daily and allowed to gain 5 g per week
Histology
Six animals failed to reach criterion for the DNMTS task and were subsequently removed from the study. Further, cannula patency was lost in two rats during the course of infusions, thus resulting in an N of 16. All 16 rats were found to have cannula placements within the MS/VDB complex (see Fig. 1A). Most of the placements straddled the midline, with the most variability being in the anterior to posterior position (see Fig. 1B, C).
Effects of intraseptal OXO on DNMTS performance: day of administration (wednesday)
Intraseptal infusions of OXO significantly decreased the number
Discussion
Infusion of OXO into the MS/VDB immediately following the to-be-remembered event resulted in a dose-dependent amnesia. This effect was evidenced by a decrease in correct entries and an increase in retroactive errors 180 min following treatment. There was also a decrease in latency-per-choice at the low (1.0 μg) and middle (5.0 μg) doses. The latter effect could be construed as a sensori-motor side effect. It seems unlikely, however that the memory deficits resulted from a drug-induced
Acknowledgements
This work is supported by NSF 0090451.
References (81)
- et al.
Chronic treatment of old rats with donepezil or galantamineeffects on memory, hippocampal plasticity and nicotinic receptors
Neuroscience
(2000) Physiology and pharmacology of hippocampal formation theta rhythms
Prog Neurobiol
(1986)Two-stage model of memory trace formationa role for “noisy” brain states
Neuroscience
(1989)- et al.
Cellular bases of hippocampal EEG in the behaving rat
Brain Res
(1983) - et al.
A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory
Neuropharmacology
(1998) - et al.
Operational dynamics in the hippocampal-entorhinal axis
Neurosci Biobehav Reviews
(1998) - et al.
Antagonism of GABAergic transmission within the septum disrupts working/episodic memory in the rat
Neuroscience
(1992) - et al.
Intraseptal administration of muscimol produces dose-dependent memory impairments in the rat
Behav Neural Biol
(1989) - et al.
Tacrine in Alzheimer's disease
Lancet
(1991) - et al.
Oxotremorine infusions into the medial septum of middle-aged rats affect spatial reference memory and ChAT activity
Behav Brain Res
(1996)
Ageingthe cholinergic hypothesis of cognitive decline
Curr Opin Neurobiol
Bidirectional modulation of scopolamine-induced working memory impairments by muscarinic activation of the medial septal area
Neurobiol Learn Mem
Acetylcholine release in the hippocampuseffects of cholinergic and GABAergic compounds in the medial septal area
Neurosci Lett
Neuromodulation and the hippocampusmemory function and dysfunction in a network simulation
Prog Brain Res
Neuromodulation, theta rhythm and rat spatial navigation
Neural Netw
Effects of intraseptal zolpidem and chlordiazepoxide on spatial working memory and high-affinity choline uptake in the hippocampus
Neurobiol Learn Mem
Intraseptal flumazenil enhances, while diazepam binding inhibitors impairs, performance in a working memory task
Neurobiol Learn Mem
The nature and causes of hippocampal long-term potentiation
Prog Brain Res
Evidence for glutamate, in addition to acetylcholine and GABA, neurotransmitter synthesis in basal forebrain neurons projecting to the entorhinal cortex
Neuroscience
Reversible inactivation of the medial septum differentially affects two forms of learning in rats
Brain Res
Elicitation of hippocampal theta by intraseptal carbachol injection in freely-moving rats
Brain Res
Characterisation of muscarinic autoreceptors in the septo-hippocampal system of the rata microdialysis study
Eur J Pharmacol
Acetylcholine, aging, and Alzheimer's disease
Pharmacol Biochem Behav
Necropsy evidence of central cholinergic deficits in senile dementia
Lancet
Glucose injections into the medial septum reverse the effects of intraseptal morphine infusions on hippocampal acetylcholine output and memory
Neuroscience
Glucose attenuates a morphine-induced decrease in hippocampal acetylcholine outputan in vivo microdialysis study in rats
Brain Res
Cortical projections arising from the basal forebraina study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase
Neuroscience
Injections of tacrine and scopolamine into the nucleus accumbensopposing effects of immediate vs delayed posttrial treatment on memory of an open field
Neurobiol Learn Mem
Donepezil-induced REM sleep augmentation enhances memory performance in elderly healthy persons
Exp Gerontol
Chlordiazepoxide-induced working memory impairmentssite specificity and reversal by flumazenil
Behav Neural Biol
Baclofen produces dose-related working memory impairments after intraseptal injection
Behav Neural Biol
The hippocampus as an associator of discontiguous events
Trends Neurosci
Muscarinic tone sustains impulse flow in the septohippocampal GABA but not cholinergic pathwayimplications for learning and memory
J Neurosci
An analysis of the origins of the cholinergic and noncholinergic septal projections to the hippocampal formation of the rat
J Comp Neurol
The cholinergic hypothesis of geriatric memory dysfunction
Science
Selective immunotoxic lesions of basal forebrain cholinergic cellseffects on learning and memory in rats
Behav Neurosci
Intact spatial learning in both young and aged rats following selective removal of hippocampal cholinergic input
Behav Neurosci
Choline acetyltransferase-immunoreactive neurons and terminals in the rat septal complexa combined light and electron microscopic study
J Comp Neurol
Forgetting of an operant responsephysostigmine-produced increases in escape latency in rats as a function of time of injection
Q J Exp Psychol
Phase precession and phase-locking of hippocampal pyramidal cells
Hippocampus
Cited by (21)
Discriminative patterns of white matter changes in Alzheimer's
2023, Psychiatry Research - NeuroimagingSwimming improves the emotional memory deficit by scopolamine via mu opioid receptors
2014, Physiology and BehaviorCitation Excerpt :Moreover, following exercise, various neurotransmitter systems (including acetylcholine, GABA, monoamines and glutamate) are shown to affect the BDNF expression in the hippocampus [91]. The hippocampus has anatomical connections with various subcortical regions, including the medial septum which is a part of the forebrain circuitry involved in memory [92,93]. Furthermore, acetylcholine is one of the brain neurotransmitters [94] which plays a crucial part in learning, memory and attention processes [95–97].
Possible interaction of cholinergic and GABAergic systems between MS and CA1 upon memory acquisition in rats
2012, Behavioural Brain ResearchCitation Excerpt :Both muscarinic and nicotinic Ach receptors have a role in new information encoding [8]. Cholinergic receptors enrich in the medial septum [9]. It has been shown that GABA inhibited Ach release in hippocampus via septal GABAA receptors [10].
Scopolamine induced memory impairment; possible involvement of NMDA receptor mechanisms of dorsal hippocampus and/or septum
2012, Behavioural Brain ResearchCitation Excerpt :The CA1 mediates neural plasticity processes involved in the acquisition, storage and retrieval of memory within the hippocampus [6]. The hippocampus has anatomical connections with various subcortical regions, including the medial septum (MS) which is a part of the forebrain circuitry involved in memory [7,8]. Furthermore, acetylcholine (ACh) is one of the brain neurotransmitters [9] involved in learning, memory and attention processes [10–12].
The cholinergic system and spatial learning
2011, Behavioural Brain ResearchCitation Excerpt :Coherent with an amelioration of age-dependent deficits, muscarinic agonists generally prevent spatial memory deficits induced by pharmacological cholinergic blockade, due to an increased activity of septo-hippocampal neurons [144,146] resulting in enhanced hippocampal ACh release [147–150]. Notably, post-acquisition administration of cholinergic drugs produced an impairment or no effect on spatial memory performance [151,152] suggesting a disruption of memory consolidation. Again, this is owed to the biphasic cholinergic demand during acquisition and retention [141].