Morphological maturation of basal forebrain cholinergic neurons

The advantage of Golgi staining is that it offers detailed morphology of individual neurons, the disadvantage being that the neurotransmitter pheno-type cannot be determined. Analyzing Golgi-stained neurons in the rat basal nucleus that display morphological features of cholinergic neurons, Gould et al. (1989) reported that basal nucleus neurons increase in cell body area, number of primary den-drites and length of dendrites, with a peak at P18. All of these values, however, decrease by P27,...

Basal forebrain cholinergic neurons and their cortical projections

As already mentioned, early studies using Nissl, myelin and Golgi stain indicated that the magnocel-lular basal nucleus or nucleus of Meynert shows phylogenetic progression in structural growth and complexity among mammalian species from rodents to human, in parallel with the evolution of the neocortex (Gorry, 1963). Obviously, the cholinergic nature of these magnocellular cells was not identified, and the observations in some species will have to be confirmed using ChAT immunohistochemistry...

KCNQtype K channels

Cloned K channels of the eag type ('ether-a-gogo') were shown to be muscarine-sensitive by Stansfeld et al. (1996). An interesting point is that they are readily blocked by a small rise in internal Ca2 +. Thus, Ca2 + could be the second messenger between these receptors and K channels (see also Selyanko and Brown, 1996). On the other hand, albeit present in cortex, eag channels may account for only part of cortical M current perhaps only a slow component (Meves et al., 1999 Selyanko et al.,...

Choline acetyltransferase in autism

The status of the cholinergic system in autism, based on basal forebrain and cortical indices in adults, is summarized in Table 1. No abnormalities are apparent in the activity of the transmitter synthesizing enzyme choline acetyltransferase (ChAT) in frontal or parietal cortex or the basal forebrain, although activity in the basal forebrain tends to be increased (Perry et al., 2001). In relation to the original neuropathological evidence of basal fore-brain cholinergic dysfunction in autism...

Interaction of anesthetics with cholinergic transmission

It is not known how general anesthetics interfere with cholinergic transmission to produce unconsciousness. One possibility is that they interfere directly and there is an extensive literature implicating both nicotinic and muscarinic mechanisms. The nicotinic acetylcholine receptor (nAChR) is one of several ligand-gated ion channels that are extremely sensitive to the inhibitory effects of a variety of anesthetics including etomidate, propofol, ketamine, barbiturates and, particularly,...

In vivo measurement of cholinergic activity in normal and Alzheimer brains

The cholinergic neurotransmitter system, which is involved in cognitive processes, is severely impaired in AD (Perry, 1986 Court et al., 2001 Nordberg, 2001). Functional imaging allows measurement of acetylcholinesterase (AchE) (Iyo et al., 1997 Kuhl et al., 1999) and butyrylcholinesterase (BuChE) activities (Snyder et al., 2001), nicotinic (Nordberg et al., 1995), muscarinic receptor binding (Dewey et al., 1990), and vesicular acetylcholine transporter (Kuhl et al., 1996) in normal subjects...

Acknowledgments of sponsorship and support

This monograph is the 24th in a series of reports based on the proceedings of an annual international symposium organized by the Centre de recherche en sciences neurologiques (CRSN) of the Universit de Montr al (UdeM). The cost of this annual meeting is partly defrayed by an operating grant of the University to the Groupe de recherche sur le systeme nerveux central (GRSNC). We also gratefully acknowledge the complementary financial support received from the Fonds de la recherche en sante du...

Propofolinduced loss of consciousness Meuret et al 2000

Propofol was administered intravenously to 17 volunteers using a computer controlled infusion pump to achieve stable plasma and CNS effector site concentration of drug. The infusion rate was determined using population-based pharmacokinetic data to achieve predictable drug concentration, and arterial blood samples were obtained for post hoc plasma concentration analysis. The rate of infusion was increased stepwise until loss of consciousness was achieved and subjects were motionless. Loss of...

Activity and the development of cortical circuits

It is now a well-established fact that neuronal activity plays an important role in the development of sensory pathways. Beginning with the work of Hubel Corresponding author Tel. 718 430 3681 Fax 718 430 8821 E-mail peinado aecom.yu.edu and Wiesel almost five decades ago, a wealth of information has accumulated in support of this notion and progress has been made toward elucidating many of the mechanisms involved (Wiesel, 1982 Katz and Shatz, 1996 Crair, 1999 Zhang and Poo, 2001). Although it...

Cholinoceptive neurons of the cerebral cortex

Incoming cholinergic axons innervate at least three kinds of cortical neurons glutamatergic neurons with nicotinic or muscarinic receptors, GABAergic inter-neurons and NADPHd-positive infracortical neurons. The one marker most closely associated with cholinoceptive neurons is acetylcholinesterase (AChE), the enzyme which terminates cholinergic neurotransmission through the rapid hydrolysis of ACh into acetate and choline. Although the vast majority of cholinoceptive neurons probably express...

Origin and migration of basal forebrain cholinergic neurons

AChE is expressed in immature BF neurons, and therefore, using this enzyme as a marker, the origin and migration of cholinergic BF neurons have been studied in the cat (Krnjevic and Silver, 1966). BF neurons appear to be derived from the ganglionic eminence (Krnjevic and Silver, 1966), a bulge on the ventricular wall that is present during early stages of telencephalic development. The ganglionic eminence also gives rise to the striatum, the globus pallidus and other subcortical structures (see...

Materials and methods

The experiments described here were done on 300400 mm-thick slices obtained from Long-Evans rats pups aged 0-15 days. The plane of section was coronal, sagital, or horizontal and, since they were taken from whole brains, included as much cortex as could be obtained in each plane. Slices were incubated in artificial CSF (aCSF) containing fura-2 AM (5 mg ml) for 1-2 h at 30 C. The composition of the aCSF, modified according to MacGregor et al. (2001), to prevent neuronal swelling was (in mM) NaCl...

References

Alkire, M.T. and Haier, R.J. (2001) Correlating in vivo anaesthetic effects with ex vivo receptor density data supports a GABAergic mechanism of action for propofol, but not for isoflurane. Br. J. Anaesth., 86 618-626. Angel, A. (1993) Central neuronal pathways and the process of anaesthesia. Br. J. Anaesth., 71 148-163. Anthony, B.L., Dennison, R.L., Narayanan, T.K. and Aronstam, R.S. (1988) Diethyl ether effects on muscarinic acetylcholine complexes in rat brainstem. Biochem. Pharmacol., 37...

Clinical and therapeutic implications of the nicotinic receptor loss in autism

It is striking that amongst a range of cholinergic activities investigated in autism, and of other transmitter activities such as dopaminergic and 5-HT1 also investigated in the same series (Perry et al., unpublished), the only consistent and extensive phenotypic abnormality is the loss of the nicotinic a4ft2 receptor subtype. Although not yet established, the nicotinic a4fi2 receptor loss from the cerebral cortex could relate to clinical features of autism, such as attentional abnormalities,...

New insights in to the neurochemistry of consciousness

In exploring a 'cholinergic hypothesis of consciousness', this chapter depends on assumptions and correlations which are admittedly highly speculative. In the first place, a broad range of human cerebral pathologies could be linked to consciousness, since so many human brain activities involves conscious awareness, from sensory perception to higher cognitive functions. Disorders such as blindsight, schizophrenia, narcolepsy, delirium, depression, Alzheimer's disease, frontotemporal dementia,...

Intracortical neurons as a local relay for integrating local perfusion to neuronal activity

Several populations of interneurons within the cerebral cortex send projections to neighboring microvessels and could modify microvascular tone. In this respect, a population of neurons with activity related to spontaneous waves of CBF has recently been identified in the cerebral cortex and is suspected of transducing neuronal signals into vasomotor responses (Golanov et al., 1994, 2000). These neurons could be involved in both the propagation and restriction of the neurally-mediated changes in...

Conclusion is central cholinergic transmission a final common pathway affected by anesthetics

Although current knowledge implicates altered central cholinergic transmission as a mediator of anesthetic-induced altered states of consciousness, our human data must be interpreted with caution. In volunteers, physostigmine clearly reversed the loss of consciousness produced by propofol and remifenta-nil. The reversal was blocked by pretreatment with scopolamine (propofol study). Physostigmine did not reliably reverse the unconsciousness produced by sevoflurane, as it did with propofol and...

Introduction

Alzheimer's disease (AD) is the most common form of dementia. It is a devastating illness affecting not only the patient, but also his family and the society. AD is a neurodegenerative disease with a relentless course, starting during healthy ageing, when only minor changes in performances of cognitive tasks are seen compared to healthy young individuals, followed by a progressive change in cognitive, affective and behavioral parameters. A great demand is presently put on available functional...