Glutamatergic Contributions to Nicotinic Acetylcholine Receptor Agonist-Evoked Cholinergic Transients in the Prefrontal Cortex

Parikh, Vinay; Man, Kingson; Decker, Michael; Sarter, Martin

doi:10.1523/jneurosci.5251-07.2008

Cited by 120 publications

(159 citation statements)

References 68 publications

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“…The neuronal mechanisms underlying the generation of cortical cholinergic transients are not well understood but involve glutamatergic signaling from thalamic afferents (36). Our current circuitry model suggests that separate cholinergic neuromodulatory activity, acting on a scale of minutes, can influence the generation of transients via stimulation of nicotinic ACh receptors expressed by thalamic glutamatergic terminals (37,38).…”

Section: Discussionmentioning

confidence: 92%

Cortical cholinergic signaling controls the detection of cues

Gritton

Howe

Mallory

et al. 2016

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

184

208

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The cortical cholinergic input system has been described as a neuromodulator system that influences broadly defined behavioral and brain states. The discovery of phasic, trial-based increases in extracellular choline (transients), resulting from the hydrolysis of newly released acetylcholine (ACh), in the cortex of animals reporting the presence of cues suggests that ACh may have a more specialized role in cognitive processes. Here we expressed channelrhodopsin or halorhodopsin in basal forebrain cholinergic neurons of mice with optic fibers directed into this region and prefrontal cortex. Cholinergic transients, evoked in accordance with photostimulation parameters determined in vivo, were generated in mice performing a task necessitating the reporting of cue and noncue events. Generating cholinergic transients in conjunction with cues enhanced cue detection rates. Moreover, generating transients in noncued trials, where cholinergic transients normally are not observed, increased the number of invalid claims for cues. Enhancing hits and generating false alarms both scaled with stimulation intensity. Suppression of endogenous cholinergic activity during cued trials reduced hit rates. Cholinergic transients may be essential for synchronizing cortical neuronal output driven by salient cues and executing cue-guided responses.V irtually all cortical regions and layers receive inputs from cholinergic neurons originating in the nucleus basalis of Meynert, the substantia innominata, and the diagonal band of the basal forebrain (BF). Reflecting the seemingly diffuse organization of this projection system, functional conceptualizations traditionally have described acetylcholine (ACh) as a neuromodulator that influences broadly defined behavioral and cognitive processes such as wakefulness, arousal, and gating of input processing (1, 2). However, anatomical studies have revealed a topographic organization of BF cholinergic cell bodies with highly segregated cortical projection patterns (3-7). Such an anatomical organization favors hypotheses describing the cholinergic mediation of discrete cognitive-behavioral processes. Studies assessing the behavioral effects of cholinergic lesions, recording from or stimulating BF neurons in behaving animals have supported such hypotheses, proposing that cholinergic activity enhances sensory coding and mediates the ability of reward-predicting stimuli to control behavior (8-17).In separate experiments using two different tasks, we reported the presence of phasic cholinergic release events (transients) in the medial prefrontal cortex (mPFC) of rodents trained to report the presence of cues (18,19). These studies used choline-sensitive microelectrodes to measure changes in extracellular choline concentrations that reflect the hydrolysis of newly released ACh by endogenous acetylcholinesterase (SI Results and Discussion). Importantly, such cholinergic transients were not observed in trials in which cues were missed and in which the absence of a cue was correctly reported and rewarded. Cho...

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Section: Discussionmentioning

confidence: 92%

Cortical cholinergic signaling controls the detection of cues

Gritton

Howe

Mallory

et al. 2016

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

184

208

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“…These data suggest that neuronal events critical to the functional maturation of this distributed system are ongoing during earlier, but not later ages of development, and that these mechanisms contribute to subsequent deficits in the modulation of cortical cholinergic transmission exhibited in PD7 rats. This impaired regulation of cortical ACh levels may reflect local changes in cortical mechanisms (Nair and Gudelsky, 2004;Parkih et al, 2008) and/or longloop, trans-synaptic changes affecting the excitability of the BFCS projections. Several mechanisms could contribute to these developmental effects.…”

Section: Age-and Regional-dependent Effects Of Ttx Infusionsmentioning

confidence: 99%

Transient Inactivation of the Neonatal Ventral Hippocampus Permanently Disrupts the Mesolimbic Regulation of Prefrontal Cholinergic Transmission: Implications for Schizophrenia

Brooks

Sarter

Bruno

2011

Neuropsychopharmacol

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These experiments determined the mesolimbic modulation of cortical cholinergic transmission in a neurodevelopmental model of schizophrenia. Mesolimbic-cholinergic abnormalities are hypothesized to contribute to the cognitive deficits seen in schizophrenia. Stimulation of NMDA receptors in nucleus accumbens (NAC) increases acetylcholine (ACh) release in the prefrontal cortex (PFC), a mechanism recently demonstrated to contribute to the control of attentional performance. We determined the ability of intra-NAC administration of NMDA to increase prefrontal ACh levels in adult rats that had received bilateral infusions of tetrodotoxin (TTX) to transiently interrupt impulse flow in the ventral hippocampus (VH) during development. Rats received infusions of TTX or saline on postnatal day 7 (PD7) or day 32 (PD32), and the effects of NAC NMDA receptor stimulation on prefrontal cholinergic neurotransmission were assessed in adulthood. In animals treated as controls on PD7, NMDA increased prefrontal ACh levels by 121% above baseline. In contrast, PD7 infusions of TTX into the VH abolished the ability of NAC NMDA to activate prefrontal cholinergic neurotransmission (7% increase). In animals that received TTX infusions on PD32, NMDA-evoked cholinergic activity did not differ from controls, indicating a restricted, neonatal critical period during which VH TTX impacts the organization of mesolimbic-basal forebrain-cortical circuitry. Importantly, the failure of NAC NMDA to evoke cholinergic activity in rats treated with TTX on PD7 did not reflect a reduced excitability of corticopetal cholinergic neurons because administration of amphetamine produced similar elevations of prefrontal ACh levels in PD7 TTX and PD7 control animals. A third series of experiments demonstrated that the effects of PD7 TTX are a specific consequence of transient disruption of impulse flow in the VH. Intra-NAC NMDA evoked prefrontal ACh release in rats receiving TTX, on PD7, into the dorsal hippocampus (DH), basolateral amygdala, or NAC. Thus, impulse flow specifically within the VH, during a sensitive period of development, is necessary for the functional organization of a mesolimbic-cortical circuit known to mediate attentional control processes. Therefore, neonatal inactivation of VH represents an effective animal model for studying the basis of certain cognitive symptoms of schizophrenia.

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“…Cholinergic projections to the PFC from the nucleus basalis of Meynert will release ACh in response to activation of α4β2* nAChRs residing on prefrontal dopaminergic and glutamatergic afferents [111,112]. The known changes in tonic to phasic release of ACh from these neurons during increased performance in a cue detection task may permit alterations in GABAergic interneuron firing, hence affecting PFC network function [113].…”

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confidence: 99%

Nicotinic acetylcholine receptors and the ascending dopamine pathways

Livingstone

Wonnacott

2009

Biochemical Pharmacology

125

114

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Nicotinic acetylcholine receptors (nAChRs) are widely expressed in midbrain dopamine neurons that project to dorsal striatum, nucleus accumbens and prefrontal cortex. Thus nAChRs can influence the functions of these three pathways; notably motor control, 'reward' and executive function, respectively. Diverse subtypes of nAChRs have been identified on dopamine cell bodies and terminals as well as on neighbouring afferents and interneurons. Here we review the molecular and cellular mechanisms through which nAChRs exert their influence on these pathways in rodents. Page 4 of 40A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 5 IntroductionThe association of nicotine with tobacco addiction has stimulated particular interest in how nicotine interacts with the 'reward' pathways of the brain. Most attention has been given to the ascending dopaminergic pathways that arise in the midbrain and project to aspects of the basal ganglia and prefrontal cortex (PFC; Fig. 1). In addition to mediating the reinforcing properties of addictive substances, dopamine is also central to the fine control of movement governed by the basal ganglia, whereas its actions in the PFC are critically important to 'executive' function [1,2]. This includes working memory, behavioural flexibility and decision making, and the PFC is also involved with the anticipation of reward [3,4]. FIGURE ONE NEAR HERENicotine interacts with the dopamine systems via nicotinic acetylcholine receptors (nAChRs), a family of ligand-gated pentameric cation channels constituted from at least nine α and β subunits (α2-7 and β2-4) expressed in the mammalian brain [5]. nAChR subtypes can differ in their sensitivities to nicotine or acetylcholine (ACh), their channel characteristics (including their propensity to desensitise) and their cellular distribution. A high relative permeability to Ca 2+ , a notable characteristic of the α7 nAChR subtype, enables nAChRs to interface with a variety of intracellular Ca 2+ -dependent mechanisms [6]. The localisation of nAChRs on dopamine cell bodies in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) allows nicotine to directly modulate dopaminergic cell firing. Additionally, nAChRs on dopamine terminals can influence transmitter release. nAChRs present on afferents projecting to the VTA and SNc or to the terminal fields can also influence the activity of dopaminergic neurons. The nicotinic modulation of dopamine release has generated interest in nAChRs as therapeutic targets for conditions involving dopaminergic dysfunction, including schizophrenia, attention deficit hyperactivity disorder, Parkinson's disease, Alzheimer's disease and age-related cognitive impairment [7][8][9][10].In this review we focus on the mechanisms through which nAChRs modulate the activity of dopamine neurones of the principal ascending pathways (Fig. 1). We will considerPage 6 of 40A c c e p t e d M a n u s c r i p t 6 nicotinic influences on somatodendritic and terminal fields, with the aim of integratin...

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Glutamatergic Contributions to Nicotinic Acetylcholine Receptor Agonist-Evoked Cholinergic Transients in the Prefrontal Cortex

Cited by 120 publications

References 68 publications

Cortical cholinergic signaling controls the detection of cues

Cortical cholinergic signaling controls the detection of cues

Transient Inactivation of the Neonatal Ventral Hippocampus Permanently Disrupts the Mesolimbic Regulation of Prefrontal Cholinergic Transmission: Implications for Schizophrenia

Nicotinic acetylcholine receptors and the ascending dopamine pathways

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