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Martin Sarter

Publications and source records attributed to Martin Sarter.

28 records · Page 2Linked to original sources
PubMed2004

Rapid assessment of in vivo cholinergic transmission by amperometric detection of changes in extracellular choline levels.

Conventional microdialysis methods for measuring acetylcholine (ACh) efflux do not provide sufficient temporal resolution to relate cholinergic transmission to individual stimuli or behavioral responses, or sufficient spatial resolution to investigate heterogeneities in such regulation within a brain region. In an effort to overcome these constraints, we investigated a ceramic-based microelectrode array designed to measure amperometrically rapid changes in extracellular choline as a marker for cholinergic transmission in the frontoparietal cortex of anesthetized rats. These microelectrodes exhibited detection limits of 300 nm for choline and selectivity (> 100 : 1) of choline over interferents such as ascorbic acid. Intracortical pressure ejections of choline (20 mm, 66-400 nL) and ACh (10 and 100 mm, 200 nL) dose-dependently increased choline-related signals that were cleared to background levels within 10 s. ACh, but not choline-induced signals, were significantly attenuated by co-ejection of the acetylcholinesterase inhibitor neostigmine (Neo; 100 mm). Pressure ejections of drugs known to increase cortical ACh efflux, potassium (KCl; 70 mm, 66, 200 nL) and scopolamine (Scop; 10 mm, 200 nL), also markedly increased extracellular choline signals, which again were inhibited by Neo. Scop-induced choline signals were also found to be tetrodotoxin-sensitive. Collectively, these findings suggest that drug-induced increases in current measured with these microelectrode arrays reflect the oxidation of choline that is neuronally derived from the release and subsequent hydrolysis of ACh. Choline signals assessed using enzyme-selective microelectrode arrays may represent a rapid, sensitive and spatially discrete measure of cholinergic transmission.

Acetylcholine↗
PubMed2003

Microdialysis without acetylcholinesterase inhibition reveals an age-related attenuation in stimulated cortical acetylcholine release.

Aging-related differences in the ability of cortical cholinergic inputs to respond to local depolarization was assessed in young (3-6 months) and old (26-33 months) awake rats using in vivo microdialysis in the absence of an inhibitor of acetylcholinesterase. Rats were perfused, using a within-subjects, repeated session design, with vehicle (aCSF) or K(+) (25, 50, 100 mM). Perfusion of K(+) resulted in a dose-dependent increase in cortical ACh efflux with comparable efflux seen between the two ages following 25 mM (50%) and 50 mM (100%) K(+). In contrast, aged rats exhibited a marked attenuation (330%) in ACh efflux relative to young adult rats (650%). These data reveal aging-related decreases in the responsiveness of cortical cholinergic afferents, tested under physiologically relevant conditions, to local depolarization and may provide a neuronal mechanism contributing to the cognitive deficits reported in normal aging- and age-related pathological conditions.

Acetylcholine↗
PubMed2003

Attentional functions of cortical cholinergic inputs: what does it mean for learning and memory?

The hypothesis that cortical cholinergic inputs mediate attentional functions and capacities has been extensively substantiated by experiments assessing the attentional effects of specific cholinotoxic lesions of cortical cholinergic inputs, attentional performance-associated cortical acetylcholine release, and the effects of pharmacological manipulations of the excitability of basal forebrain corticopetal cholinergic projections on attentional performance. At the same time, numerous animal experiments have suggested that the integrity of cortical cholinergic inputs is not necessary for learning and memory, and a dissociation between the role of the cortical cholinergic input system in attentional functions and in learning and memory has been proposed. We speculate that this dissociation is due, at least in part, to the use of standard animal behavioral tests for the assessment of learning and memory which do not sufficiently tax defined attentional functions. Attentional processes and the allocation of attentional capacities would be expected to influence the efficacy of the acquisition and recall of declarative information and therefore, persistent abnormalities in the regulation of the cortical cholinergic input system may yield escalating impairments in learning and memory. Furthermore, the cognitive effects of loss of cortical cholinergic inputs are augmented by the disruption of the top-down regulation of attentional functions that normally acts to optimize information processing in posterior cortical areas. Because cortical cholinergic inputs play an integral role in the mediation of attentional processing, the activity of cortical cholinergic inputs is hypothesized to also determine the efficacy of learning and memory.

Attention↗
PubMed2003

Ascending visceral regulation of cortical affective information processing.

Over a century ago, William James proposed that strong emotions represent the perceptual consequences of somato-visceral feedback. Although the strong form of this conception is no longer viable, considerable evidence has accumulated indicating a range of visceral influences on higher neurobehavioural processes. This literature has only recently begun to consolidate, because earlier reports generally remained at the demonstration level, and pathways and mechanisms for such influences were uncertain. Recently, specific effects of visceral feedback have become apparent on cortical activity, cerebral auditory-evoked responses, anxiety, memory and behavioural aspects of immunological sickness. Moreover, considerable progress has been made recently in determining the specific neural pathways and systems underlying these actions, especially the role of noradrenergic projections from the nucleus of the tractus solitarius and the locus coeruleus to the amygdala in memory processes, and to the basal forebrain in the processing of anxiety-related information. The present paper highlights selected recent findings in this area, and outlines relevant structures and pathways involved in the ascending visceral influence on higher neurobehavioural processes.

Affect↗
PubMed2002

Sensitization of cortical acetylcholine release by repeated administration of nicotine in rats.

RATIONALE: The integrity of cortical cholinergic transmission is vital to attentional processing. A growing literature suggests that alterations in attentional processing accompany addictive drug use. This study examined the effects of acute and repeated administration of nicotine on cortical acetylcholine release. OBJECTIVES: The effects of repeated systemic nicotine administration on cortical acetylcholine (ACh) efflux in the frontal cortex were determined to test the hypothesis that repeated administration of nicotine results in a potentiated or sensitized increase in ACh efflux. METHODS: Animals were injected with nicotine (0.4 mg/kg, i.p.) or vehicle twice daily for 4 days. Cortical ACh efflux was measured using repeated microdialysis sampling on four occasions: on day 1, during the first exposure to nicotine or vehicle, on day 5 during a final exposure to nicotine, on day 8 during a nicotine challenge, and again on day 10 following saline administration. RESULTS: Acute nicotine administration on day 1 produced a 90% increase in cortical ACh efflux. Repeated exposure to nicotine resulted in a larger increase in cortical ACh efflux on day 5 (200%) and day 8 (210%) relative to ACh levels measured on day 1, and relative to animals that received vehicle during the initial treatment period. Cortical ACh efflux following acute nicotine administration was blocked by mecamylamine (1.0 mg/kg, i.p.). However, the sensitized efflux of cortical ACh on day 8 was only partially attenuated by mecamylamine (1.0 or 5.0 mg/kg, i.p.), suggesting a mecamylamine-insensitive component of the sensitized response to repeated nicotine administration. CONCLUSIONS: Repeated administration of nicotine results in a sensitized increase in cortical ACh release. Sensitized cortical ACh release may mediate, in part, the cognitive components of nicotine addiction.

Acetylcholine↗
PubMed2002

Effects of acute and repeated systemic administration of ketamine on prefrontal acetylcholine release and sustained attention performance in rats.

RATIONALE: The effects of non-competitive N-methyl- D-aspartate (NMDA) receptor antagonists model aspects of schizophrenic symptomatology. Because effects on both cortical cholinergic transmission and attentional processes have been hypothesized to represent components of the properties of psychotogenic drugs, the present study investigated the effects of ketamine on the activity of cortical cholinergic inputs and attentional performance. OBJECTIVE: To determine the effects of acute and repeated ketamine administration on cortical acetylcholine release and performance of rats in an operant task designed to assess sustained attention performance. METHODS: Experiment 1 assessed the effects of ketamine (2.0-20.0 mg/kg, i.p.) on medial prefrontal acetylcholine release using in vivo microdialysis. In experiment 2, animals were pretreated with 2.0 mg/kg or 25.0 mg/kg ketamine for 7 days. Cortical acetylcholine release was assessed in these rats following the subsequent administration of a 'challenge' dose of 2.0 mg/kg on days 1, 8, and 15 following completion of the pretreatment regimen. Experiment 3 assessed the effects of acute ketamine administration (2.0, 4.0, and 8.0 mg/kg, i.p.) on sustained attention performance. In experiment 4, animals trained in the sustained attention task were pretreated with 25.0 mg/kg ketamine or vehicle for 7 days. In these animals, the performance effects of 2.0 mg/kg ketamine administered 1, 8, or 15 days after completion of the pretreatment regimen were assessed. RESULTS: The acute administration of ketamine dose dependently increased cortical acetylcholine release by up to 250% above baseline and for over 40 min following the highest dose of ketamine. Pretreatment with 2.0 mg or 25.0 mg/kg did not robustly alter the effects of subsequent ketamine administration on cortical acetylcholine release. In animals performing the sustained attention task, administration of the highest dose of ketamine resulted in high levels of errors of omission, while the administration of the two smaller doses did not affect performance. Pretreatment with 25.0 mg/kg disrupted the attentional performance during the pretreatment period, but it did not affect the baseline performance thereafter. Furthermore, ketamine pretreatment did not systematically alter the performance effects of subsequent ketamine administration. CONCLUSIONS: The robust stimulation of cortical acetylcholine release represents a potent component of the pharmacological effects of ketamine. The effects of acute ketamine on attentional performance were limited to high rates of omissions. Repeated ketamine administration 'sensitized' neither cortical acetylcholine release nor attentional performance. These effects of repeated ketamine differ substantially from those of another major psychotogenic drug, amphetamine, and thus support the view that ketamine and amphetamine model fundamentally different aspects of schizophrenia.

Acetylcholine↗
PubMed2002

The neglected constituent of the basal forebrain corticopetal projection system: GABAergic projections.

At least half of the basal forebrain neurons which project to the cortex are GABAergic. Whilst hypotheses about the attentional functions mediated by the cholinergic component of this corticopetal projection system have been substantiated in recent years, knowledge about the functional contributions of its GABAergic branch has remained extremely scarce. The possibility that basal forebrain GABAergic neurons that project to the cortex are selectively contacted by corticofugal projections suggests that the functions of the GABAergic branch can be conceptualized in terms of mediating executive aspects of cognitive performance, including the switching between multiple input sources and response rules. Such speculations gain preliminary support from the effects of excitotoxic lesions that preferentially, but not selectively, target the noncholinergic component of the basal forebrain corticopetal system, on performance in tasks involving demands on cognitive flexibility. Progress in understanding the cognitive functions of the basal forebrain system depends on evidence regarding its main noncholinergic components, and the generation of such evidence is contingent on the development of methods to manipulate and monitor selectively the activity of the GABAergic corticopetal projections.

Animals↗
PubMed2002

Stimulation of cortical acetylcholine release following blockade of ionotropic glutamate receptors in nucleus accumbens.

In vivo microdialysis techniques were used to determine the ability of glutamate receptors within the nucleus accumbens to trans-synaptically modulate the basal forebrain cortical cholinergic system. Rats were implanted with a dialysis probe in the medial prefrontal cortex to measure changes in cortical acetylcholine efflux and in the ipsilateral nucleus accumbens to locally manipulate glutamate receptor activity. Intra-accumbens perfusion of the broad spectrum ionotropic glutamate receptor antagonist kynurentate (1.0, 5.0 mm) led to a dose-dependent increase (maximum of 200%) in cortical acetylcholine efflux. This stimulated efflux was reproduced with the intra-accumbens perfusion of the AMPA/kainate antagonist DNQX (0.1, 0.25, 2.5 mm; maximum increase of 200%) or the NMDA antagonist D-CPP (10.0, 100.0, 200 micro M; maximum increase of 400%). These results reveal a significant glutamatergic tone within the accumbens of awake rats and support the hypothesis that accumbens efferents to basal forebrain modulate the excitability of the basal forebrain cortical cholinergic system.

Acetylcholine↗
PubMedDate not supplied

Interactions between aging and cortical cholinergic deafferentation on attention.

Pre-existing trauma to basal forebrain corticopetal cholinergic neurons has been hypothesized to render this system vulnerable to age-related processes. The present longitudinal study assessed the interactions between the effects of partial cortical cholinergic deafferentation and aging on sustained attention performance. After pre-surgical training, animals were given sham-surgery or bilateral infusions of the immunotoxin 192 IgG-saporin into the basal forebrain. The lesion was intended to yield a limited loss of cortical cholinergic inputs and thus to produce minor immediate effects on sustained attention performance. All animals were tested continuously until age 36 months. The attentional performance of lesioned and sham-lesioned animals did not dissociate until age 31 months, when the lesioned animals exhibited an impairment in overall sustained attention performance. Importantly, this impairment interacted with the effects of time-on-task, and thus reflected a specific impairment in attentional processes. These results support the notion that pre-existing damage to the basal forebrain corticopetal cholinergic neurons yields age-related impairments in the attentional capabilities that depend on the integrity of this neuronal system.

Afferent Pathways↗