The cholinergic system and hippocampal plasticity.
ABSTRACT Acetylcholine is an essential excitatory neurotransmitter in the central nervous system and undertakes a vital role in cognitive function. Consequently, there is ample evidence to suggest the involvement of both nicotinic and muscarinic acetylcholine receptors in the modulation of synaptic plasticity, which is believed to be the molecular correlate of learning and memory. In the hippocampus in particular, multiple subtypes of both nicotinic and muscarinic receptors are present at presynaptic and postsynaptic loci of both principal neurons and inhibitory interneurons, where they exert profound bi-directional influences on synaptic transmission. Further evidence points to a role for cholinergic activation in the induction and maintenance of synaptic plasticity, and key influences on hippocampal network oscillations. The present review examines these multiple roles of acetylcholine in hippocampal plasticity.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: A substantial number of studies on basal forebrain (BF) cholinergic neurons (BFCN) have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer's disease (AD), and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA) axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine (ACh), glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, to which could help decipher disease states and propose leads for pharmacological intervention.Frontiers in Aging Neuroscience 04/2015; 7(doi: 10.3389/fnagi.2015.00043). DOI:10.3389/fnagi.2015.00043 · 2.84 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Most individuals with schizophrenia suffer some cognitive dysfunction: such deficits are predictive of longer-term functioning; and current dopamine-blocking antipsychotics have made little impact on this domain. There is a pressing need to develop novel pharmacological agents to tackle this insidious but most disabling of problems. The acetylcholinergic system is involved in cognitive and attentional processing, and its metabotropic and nicotinic receptors are widespread throughout the brain. Deficits in acetylcholinergic functioning occur in schizophrenia, and high rates of tobacco smoking have been posited to represent a form of self-medication. The nicotinic acetylcholine receptor (nAChR) has emerged as a putative target to improve cognitive deficits in schizophrenia, and this study systematically reviewed the emerging data. Nineteen studies were identified, covering three compound classes: agonists at the α7 and α 4β2 nAChRs, and positive allosteric modulators. Overall data are underwhelming: some studies showed significant improvements in cognition but as many studies had negative findings. It remains unclear if this represents drug limitations or nascent study methodology problems. The literature is particularly hindered by variability in inclusion of smokers, generally small sample sizes, and a lack of consensus on cognitive test batteries. Future work should evaluate longer-term outcomes, and, particularly, the effects of concomitant cognitive training. © The Author(s) 2015.Journal of Psychopharmacology 01/2015; 29(2). DOI:10.1177/0269881114564096 · 2.81 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Transcranial Direct Current Stimulation (tDCS) is emerging as a versatile tool to affect brain function. While acute neurophysiological effects of stimulation are well understood, little is know about the long term effects. One hypothesis is that stimulation modulates ongoing neural activity which then translates into lasting effects via physiological plasticity. Here we used carbachol-induced gamma oscillations in hippocampal rat slices to establish whether prolonged constant current stimulation has a lasting effect on endogenous neural activity. During 10 minutes of stimulation, power and frequency of gamma oscillations, as well as multi-unit activity were modulated in a polarity specific manner. Remarkably, the effects on power and multi-unit activity persisted for more than 10 minutes after stimulation terminated. Using a computational model we propose that altered synaptic efficacy in excitatory and inhibitory pathways could be the source of these lasting effects. Future experimental studies using this novel in-vitro preparation may be able to confirm or refute the proposed hypothesis. Copyright © 2014, Journal of Neurophysiology.Journal of Neurophysiology 12/2014; DOI:10.1152/jn.00208.2014 · 3.04 Impact Factor