The organization and possible functions of basal forebrain and pontine cholinergic systems are reviewed. Whereas the basal forebrain cholinergic neuronal projections likely subserve a common electrophysiological function, e.g. to boost signal-to-noise ratios in cortical target areas, this function has different effects on psychological processes dependent upon the neural network operations within these various cortical domains. Evidence is presented that (a) the nucleus basalis-neocortical cholinergic system contributes greatly to visual attentional function, but not to mnemonic processes per se; (b) the septohippocampal projection is involved in the modulation of short-term spatial (working) memory processes, perhaps by prolonging the neural representation of external stimuli within the hippocampus; and (c) the diagonal band-cingulate cortex cholinergic projection impacts on the ability to utilize response rules through conditional discrimination. We also suggest that nucleus basalis-amygdala cholinergic projections have a role in the retention of affective conditioning while brainstem cholinergic projections to the thalamus and midbrain dopamine neurons affect basic arousal processes (e.g. sleep-wake cycle) and behavioral activation, respectively. The possibilities and limitations of therapeutic interventions with procholinergic drugs in patients with Alzheimer's disease and other neurodegenerative disorders in which basal forebrain cholinergic neurons degenerate are also discussed.

Central cholinergic systems and cognition

Little is known about the mechanisms that allow the cortex to selectively improve the neural representations of behaviorally important stimuli while ignoring irrelevant stimuli. Diffuse neuromodulatory systems may facilitate cortical plasticity by acting as teachers to mark important stimuli. This study demonstrates that episodic electrical stimulation of the nucleus basalis, paired with an auditory stimulus, results in a massive progressive reorganization of the primary auditory cortex in the adult rat. Receptive field sizes can be narrowed, broadened, or left unaltered depending on specific parameters of the acoustic stimulus paired with nucleus basalis activation. This differential plasticity parallels the receptive field remodeling that results from different types of behavioral training. This result suggests that input characteristics may be able to drive appropriate alterations of receptive fields independently of explicit knowledge of the task. These findings also suggest that the basal forebrain plays an active instructional role in representational plasticity.

https://science.sciencemag.org/content/sci/279/5357/1714.full.pdf

Cortical map reorganization enabled by nucleus basalis activity.

A monograph communicating the current realities and future possibilities of unifying basic studies on anatomy and cellular physiology with investigations of the behavioral and physiological events of waking and sleep. Steriade established the Laboratory of Neurophysiology at Laval U., Quebec; McCarl

Brainstem control of wakefulness and sleep

Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity.

The cognitive neuroscience of sustained attention: where top-down meets bottom-up.

1. Of the sample of 322 neurons located in somatosensory cortex and tested for their responsiveness to somatic stimulation, 91 (28%) responded to stimuli applied to the skin. The majority were located in the middle cortical layers. Each of the cells subjected to tests with glutamate and acetylcholine (ACh) was rapidly adapting to cutaneous stimuli, giving a response at the onset of skin indentation and sometimes after the stimulus withdrawal. 2. Of the 30 cells tested by pairing basal forebrain (BF) stimulation with cutaneous stimulation. 18 (60%) displayed enhanced responses to the same cutaneous stimulus after the pairing. These effects lasted for greater than 5 min in 17 cases, persisting for as long as the cell was studied, sometimes greater than 1 h. 3. The enhanced responsiveness to cutaneous stimuli could not be reversed by atropine, but in each of the 11 cells where atropine was administered while the BF stimulus was paired with the skin stimulus, the pairing produced no enhancement. 4. We conclude that pairing a BF stimulus with a cutaneous stimulus leads to long-term facilitation of the responsiveness of the cortical neuron subjected to this treatment and that this effect is mediated by the release of acetylcholine from BF cholinergic neurons that act on muscarinic receptors found on neurons in the somatosensory cortex.

Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. ii, cortical neurons excited by somatic stimuli

Acetylcholine permits long-term enhancement of neuronal responsiveness in cat primary somatosensory cortex.

1. Two-hundred and seven neurons were examined for changes in their responsiveness during the iontophoretic administration of acetylcholine (ACh) in barbiturate-anesthetized cats. 2. The laminar locations of 78 cells were determined. Cholinoceptive neurons were found in all cortical layers and ranged from 50% of the cells tested in layer I to 78% in layer VI. 3. When the responsiveness of a neuron was measured by the magnitude of the discharge generated by a fixed dose of glutamate, 30 of 47 cases (64%) were potentiated, and 4 (8%) were depressed when ACh was administered during glutamate-induced excitation. 4. ACh administered during glutamate excitation was significantly more effective in altering neuronal responsiveness than was ACh administered alone (P less than 0.001). 5. When the responsiveness of a neuron was measured by the magnitude of the discharge generated by a standard somatic stimulus applied to the receptive field, 42 of 52 cases (81%) were potentiated during ACh application. This was again different from ACh treatment alone where only 4 of 27 tests (15%) resulted in subsequent enhancement of the response to somatic stimuli. 6. ACh generally increased the responsiveness of neurons with peripheral receptive fields and caused the appearance of a receptive field in some cells lacking one. 7. In many cases the changes in excitability, as measured by responses either to glutamate or to somatic stimulation, remained for prolonged time periods. When glutamate was used to test excitability, 34% (16 of 47) of the enhancements lasted more than 5 min. When somatic stimuli were used 29% (15 of 52) lasted more than 5 min. With both measures some neurons still displayed enhanced responses more than 1 h after the treatment with ACh. 8. ACh appears to act as a permissive agent that allows modification of the effectiveness with which previously existing afferent inputs drive somatosensory cortical neurons. 9. This mechanism to alter neuronal responsiveness has many of the characteristics necessary to account for the reorganization observed in somatosensory cortex following alterations in its afferent drive and may be related to some forms of learning and memory.

Transient and prolonged effects of acetylcholine on responsiveness of cat somatosensory cortical neurons.

1. Two-hundred thirty-three single neurons were isolated and studied in somatosensory cortex of cats anesthetized with pentobarbital sodium or urethane. Two-hundred and three were studied during iontophoretic administration of acetylcholine (ACh), 173 during administration of glutamate, and 24 during administration of atropine. 2. Fifty-six percent of the 218 neurons tested responded to somatic stimuli. Another 21% did so during glutamate administration. In 11 cases ACh iontophoresis uncovered a receptive field in a previously unresponsive cell. 3. Forty-six percent of the 160 cells tested responded to thalamic stimulation. Another 17% did so in the presence of glutamate, but 19 cells responded to neither cutaneous nor thalamic stimuli. 4. Sixteen percent of the 203 cells tested were overtly excited by ACh and the responses to somatic stimulation of 29% were modulated by administration of ACh. Cells displaying overt excitation and/or modulation of responses were said to be cholinoceptive and made up 39% of the sample. These cells were located in all cortical layers. 5. Cholinoceptive neurons were more likely than noncholinoceptive cells to be driven by thalamic stimulation. 6. The changes observed during ACh administration tended to be facilitatory: an enhanced responsiveness to somatic stimuli, an increased firing rate, or an increased receptive-field size. However, in 10 of the 203 cases tested one or more of these variables decreased. 7. The enhanced responsiveness during ACh administration was a robust phenomenon; responses were often increased by as much as 200% and the discharge pattern was altered so that bursts of impulses following stimulation were more common. 8. ACh tended to enhance one attribute of a cell selectively rather than to act as a general excitant. 9. ACh is a powerful neuromodulatory agent in somatosensory cortex that, when released in specific behavioral states, should enhance the responsiveness of cortical neurons.

The effects of acetylcholine on response properties of cat somatosensory cortical neurons.

Somatosensory cortex reorganizes following restricted deafferentation so that deprived neurons acquire new receptive fields. Electrophysiological data suggest that a decrease in inhibition might be one of the mechanisms contributing to these changes. This hypothesis was tested by evaluating quantitatively glutamic acid decarboxylase (GAD) immunoreactivity and cytochrome oxidase (CO) activity in normal and partially deafferented rat hindlimb somatosensory cortex. In normal animals, there were laminar differences in the frequencies of GAD+ cells that correlated with the levels of CO activity. Two weeks after transection of the sciatic nerve, CO levels were reduced in all layers of the hindlimb somatosensory cortex contralateral to the nerve transection whereas the frequencies of GAD+ cells were unchanged except in layer IV where a 16% decrease was observed. This observation is consistent with the hypothesis that the expression of GAD in layer IV is partially controlled by the amount of afferent input. The ability of novel inputs to develop stable patterns of excitation in deafferented somatosensory cortex may depend upon the reduction of GABAergic inhibition which follows deafferentation.

Quantitative study of glutamic acid decarboxylase-immunoreactive neurons and cytochrome oxidase activity in normal and partially deafferented rat hindlimb somatosensory cortex.

N. Tremblay

Papers

Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. ii, cortical neurons excited by somatic stimuli

Acetylcholine permits long-term enhancement of neuronal responsiveness in cat primary somatosensory cortex.

Transient and prolonged effects of acetylcholine on responsiveness of cat somatosensory cortical neurons.

The effects of acetylcholine on response properties of cat somatosensory cortical neurons.

Quantitative study of glutamic acid decarboxylase-immunoreactive neurons and cytochrome oxidase activity in normal and partially deafferented rat hindlimb somatosensory cortex.