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Jack Waters - One of the best experts on this subject based on the ideXlab platform.
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physiological properties of cholinergic and non cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis
PLOS ONE, 2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:Background The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. Methodology/Principal Findings Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70–80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64±3.4 and 75±2 mV; half widths 0.52±0.04 and 0.33±0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3±2.2 and 3.6±0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of ∼20 Hz and >120 Hz). Conclusions/Significance Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse.
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Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis.
PloS one, 2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:BACKGROUND The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. METHODOLOGY/PRINCIPAL FINDINGS Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70-80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64+/-3.4 and 75+/-2 mV; half widths 0.52+/-0.04 and 0.33+/-0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3+/-2.2 and 3.6+/-0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of approximately 20 Hz and >120 Hz). CONCLUSIONS/SIGNIFICANCE Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse.
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Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis.
Public Library of Science (PLoS), 2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown.Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70-80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64+/-3.4 and 75+/-2 mV; half widths 0.52+/-0.04 and 0.33+/-0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3+/-2.2 and 3.6+/-0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of approximately 20 Hz and >120 Hz).Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse
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Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis. PLoS One 5:e11046. doi: 10.1371/journal. pone.0011046
2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:Background: The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. Methodology/Principal Findings: Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70–80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 6463.4 and 7562 mV; half widths 0.5260.04 and 0.3360.02 ms). Cholinergic neurons displayed a more pronounced slow afterhyperpolarization than non-cholinergic neurons (13.362.2 and 3.660.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of,20 Hz and.120 Hz)
Tristan Hedrick - One of the best experts on this subject based on the ideXlab platform.
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physiological properties of cholinergic and non cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis
PLOS ONE, 2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:Background The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. Methodology/Principal Findings Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70–80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64±3.4 and 75±2 mV; half widths 0.52±0.04 and 0.33±0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3±2.2 and 3.6±0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of ∼20 Hz and >120 Hz). Conclusions/Significance Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse.
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Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis.
PloS one, 2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:BACKGROUND The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. METHODOLOGY/PRINCIPAL FINDINGS Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70-80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64+/-3.4 and 75+/-2 mV; half widths 0.52+/-0.04 and 0.33+/-0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3+/-2.2 and 3.6+/-0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of approximately 20 Hz and >120 Hz). CONCLUSIONS/SIGNIFICANCE Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse.
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Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis.
Public Library of Science (PLoS), 2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown.Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70-80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64+/-3.4 and 75+/-2 mV; half widths 0.52+/-0.04 and 0.33+/-0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3+/-2.2 and 3.6+/-0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of approximately 20 Hz and >120 Hz).Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse
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Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis. PLoS One 5:e11046. doi: 10.1371/journal. pone.0011046
2010Co-Authors: Tristan Hedrick, Jack WatersAbstract:Background: The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. Methodology/Principal Findings: Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70–80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 6463.4 and 7562 mV; half widths 0.5260.04 and 0.3360.02 ms). Cholinergic neurons displayed a more pronounced slow afterhyperpolarization than non-cholinergic neurons (13.362.2 and 3.660.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of,20 Hz and.120 Hz)
Martin Sarter - One of the best experts on this subject based on the ideXlab platform.
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Modes and Models of Forebrain Cholinergic Neuromodulation of Cognition
Neuropsychopharmacology, 2011Co-Authors: Michael E Hasselmo, Martin SarterAbstract:As indicated by the profound cognitive impairments caused by cholinergic receptor antagonists, cholinergic neurotransmission has a vital role in cognitive function, specifically attention and memory encoding. Abnormally regulated cholinergic neurotransmission has been hypothesized to contribute to the cognitive symptoms of neuropsychiatric disorders. Loss of cholinergic neurons enhances the severity of the symptoms of dementia. Cholinergic receptor agonists and acetylcholinesterase inhibitors have been investigated for the treatment of cognitive dysfunction. Evidence from experiments using new techniques for measuring rapid changes in cholinergic neurotransmission provides a novel perspective on the cholinergic regulation of cognitive processes. This evidence indicates that changes in cholinergic modulation on a timescale of seconds is triggered by sensory input cues and serves to facilitate cue detection and attentional performance. Furthermore, the evidence indicates cholinergic induction of evoked intrinsic, persistent spiking mechanisms for active maintenance of sensory input, and planned responses. Models have been developed to describe the neuronal mechanisms underlying the transient modulation of cortical target circuits by cholinergic activity. These models postulate specific locations and roles of nicotinic and muscarinic acetylcholine receptors and that cholinergic neurotransmission is controlled in part by (cortical) target circuits. The available evidence and these models point to new principles governing the development of the next generation of cholinergic treatments for cognitive disorders.
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glutamatergic contributions to nicotinic acetylcholine receptor agonist evoked cholinergic transients in the prefrontal cortex
The Journal of Neuroscience, 2008Co-Authors: Vinay Parikh, Michael W. Decker, Martin SarterAbstract:Because modulation of cortical cholinergic neurotransmission has been hypothesized to represent a necessary mechanism mediating the beneficial cognitive effects of nicotine and nicotinic acetylcholine receptor (nAChR) subtype-selective agonists, we used choline-sensitive microelectrodes for the real-time measurement of ACh release in vivo , to characterize cholinergic transients evoked by nicotine and the α4β2*-selective nAChR partial agonist 2-methyl-3-(2-( S )-pyrrolindinylmethoxy)pyridine dihydrochloride (ABT-089), a clinically effective cognition enhancer. In terms of cholinergic signal amplitudes, ABT-089 was significantly more potent than nicotine in evoking ACh cholinergic transients. Moreover, cholinergic signals evoked by ABT-089 were characterized by faster signal rise time and decay rate. The nAChR antagonist mecamylamine attenuated the cholinergic signals evoked by either compound. Cholinergic signals evoked by ABT-089 were more efficaciously attenuated by the relatively β2*-selective nAChR antagonist dihydro-β-erythroidine. The α7 antagonist methyllycaconitine did not affect choline signal amplitudes but partly attenuated the relatively slow decay rate of nicotine-evoked cholinergic signals. Furthermore, the AMPA receptor antagonist DNQX as well as the NMDA receptor antagonist APV more potently attenuated cholinergic signals evoked by ABT-089. Using glutamate-sensitive microelectrodes to measure glutamatergic transients, ABT-089 was more potent than nicotine in evoking glutamate release. Glutamatergic signals were highly sensitive to tetrodotoxin-induced blockade of voltage-regulated sodium channels. Together, the present evidence indicates that compared with nicotine, ABT-089 evokes more potent and sharper cholinergic transients in prefrontal cortex. Glutamatergic mechanisms necessarily mediate the cholinergic effects of nAChR agonists in the prefrontal cortex.
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Cholinergic mediation of attention: contributions of phasic and tonic increases in prefrontal cholinergic activity.
Annals of the New York Academy of Sciences, 2008Co-Authors: Vinay Parikh, Martin SarterAbstract:Contrary to the classic description of acetylcholine (ACh) as a slowly acting neuromodulator that influences arousal states, results from experiments that employed enzyme-selective microelectrodes for the real-time monitoring of ACh release in the cortex of attentional task-performing rats indicate that cholinergic signals manifesting on multiple timescales (seconds, tens of seconds, and minutes) support, and are necessary for, the mediation of defined cognitive operations. Specifically, in the prefrontal cortex, second-based cholinergic signals support the detection of behaviorally significant cues. In contrast to these prefrontal cholinergic transients, performance-associated cholinergic activity that manifested at lower temporal resolution also was observed elsewhere in the cortex. Although tonic cholinergic signal levels were correlated with the amplitudes of cue-evoked cholinergic transients, and the latter with response latencies, the interrelationships and interactions between the multiple cholinergic signaling modes remains unclear. Hypotheses concerning the afferent circuitry contributing to the regulation of second- versus minute-based cholinergic signals are discussed. The discovery of cholinergic transients and their crucial role in cue detection and attentional performance form the basis for new hypotheses about the nature of cholinergic dysfunction in cognitive disorders and offer new targets for the development of treatments for the cognitive symptoms of neuropsychiatric and neurodegenerative disorders.
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prefrontal acetylcholine release controls cue detection on multiple timescales
Neuron, 2007Co-Authors: Vinay Parikh, Rouba Kozak, Vicente Martinez, Martin SarterAbstract:Cholinergic neurons originating from the basal forebrain innervate the entire cortical mantle. Choline-sensitive microelectrodes were used to measure the synaptic release of cortical acetylcholine (ACh) at a subsecond resolution in rats performing a task involving the detection of cues. Cues that were detected, defined behaviorally, evoked transient increases in cholinergic activity (at the scale of seconds) in the medial prefrontal cortex (mPFC), but not in a nonassociational control region (motor cortex). In trials involving missed cues, cholinergic transients were not observed. Cholinergic deafferentation of the mPFC, but not motor cortex, impaired cue detection. Furthermore, decreases and increases in precue cholinergic activity predicted subsequent cue detection or misses, respectively. Finally, cue-evoked cholinergic transients were superimposed over slower (at the timescale of minutes) changes in cholinergic activity. Cortical cholinergic neurotransmission is regulated on multiple timescales to mediate the detection of behaviorally significant cues and to support cognitive performance.
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unraveling the attentional functions of cortical cholinergic inputs interactions between signal driven and cognitive modulation of signal detection
Brain Research Reviews, 2005Co-Authors: Martin Sarter, Michael E Hasselmo, John P Bruno, Ben GivensAbstract:Neurophysiological studies demonstrated that increases in cholinergic transmission in sensory areas enhance the cortical processing of thalamic inputs. Cholinergic activity also suppresses the retrieval of internal associations, thereby further promoting sensory input processing. Behavioral studies documented the role of cortical cholinergic inputs in attentional functions and capacities by demonstrating, for example, that the integrity of the cortical cholinergic input system is necessary for attentional performance, and that the activity of cortical cholinergic inputs is selectively enhanced during attentional performance. This review aims at integrating the neurophysiological and behavioral evidence on the functions of cortical cholinergic inputs and hypothesizes that the cortical cholinergic input system generally acts to optimize the processing of signals in attention-demanding contexts. Such signals drecruitT, via activation of basal forebrain corticopetal cholinergic projections, the cortical attention systems and thereby amplify the processing of attentiondemanding signals (termed dsignal-driven cholinergic modulation of detectionT). The activity of corticopetal cholinergic projections is also modulated by direct prefrontal projections to the basal forebrain and, indirectly, to cholinergic terminals elsewhere in the cortex; thus, cortical cholinergic inputs are also involved in the mediation of top-down effects, such as the knowledge-based augmentation of detection (see Footnote 1) of signals and the filtering of irrelevant information (termed dcognitive cholinergic modulation of detectionT). Thus, depending on the quality of signals and task characteristics, cortical cholinergic activity reflects the combined effects of signaldriven and cognitive modulation of detection. This hypothesis begins to explain signal intensity or duration-dependent performance in attention tasks, the distinct effects of cortex-wide versus prefrontal cholinergic deafferentation on attention performance, and it generates specific predictions concerning cortical acetylcholine (ACh) release in attention task-performing animals. Finally, the consequences of abnormalities in the regulation of cortical cholinergic inputs for the manifestation of the symptoms of major neuropsychiatric disorders are conceptualized in terms of dysregulation in the signal-driven and cognitive cholinergic modulation of detection processes.
Frances M. Leslie - One of the best experts on this subject based on the ideXlab platform.
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Co-expression of α7 and β2 nicotinic acetylcholine receptor subunit mRNAs within rat brain cholinergic neurons
Neuroscience, 2003Co-Authors: Layla Azam, Ursula H. Winzer-serhan, Frances M. LeslieAbstract:Nicotine enhances cognitive and attentional processes through stimulation of the basal forebrain cholinergic system. Although muscarinic cholinergic autoreceptors have been well characterized, pharmacological characterization of nicotinic autoreceptors has proven more difficult. The present study used double-labeling in situ hybridization to determine expression of nicotinic acetylcholine receptor (nAChR) subunit mRNAs within basal forebrain cholinergic neurons in order to gain information about possible nAChR autoreceptor properties. Cholinergic cells of the mesopontine tegmentum and striatal interneurons were also examined, as were septohippocampal GABAergic neurons that interact with cholinergic neurons to regulate hippocampal activity. alpha7 and beta2 nAChR mRNAs were found to be co-expressed in almost all cholinergic cells and in the majority of GABAergic neurons examined. alpha4 nAChR mRNA expression was restricted to cholinergic cells of the nucleus basalis magnocellularis, and to non-cholinergic cells of the medial septum and mesopontine tegmentum. These data suggest possible regional differences in the pharmacological properties of nicotinic autoreceptors on cholinergic cells. Whereas most cholinergic cells express rapidly desensitizing alpha7 homomers or alpha7beta2 heteromers, cortical projection neurons may also express a pharmacologically distinct alpha4beta2 nAChR subtype. There may also be differential nAChR regulation of cholinergic and non-cholinergic cells within the mesopontine tegmentum that are implicated in acquisition of nicotine self-administration.
Kathryn Allaway - One of the best experts on this subject based on the ideXlab platform.
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cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain
eLife, 2020Co-Authors: Kathryn Allaway, William Munoz, Robin Tremblay, Mia Sherer, Jacob HerronAbstract:The basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the mouse cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.
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cellular birthdate predicts laminar and regional cholinergic projection topography in the forebrain
bioRxiv, 2020Co-Authors: Kathryn Allaway, William Munoz, Robin Tremblay, Mia Sherer, Jacob HerronAbstract:Abstract The basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.