Contribution of acetylcholine to visual cortex plasticity

Acetylcholine is involved in a variety of brain functions. In the visual cortex, the pattern of cholinergic innervation varies considerably across different mammalian species and across different cortical layers within the same species. The physiological effects of acetylcholine in the visual cortex display complex responses, which are likely due to cholinergic receptor subtype composition in cytoplasm membrane as well as interaction with other transmitter systems within the local neural circuitry. The functional role of acetylcholine in visual cortex is believed to improve the signal-to-noise ratio of cortical neurons during visual information processing. Available evidence suggests that acetylcholine is also involved in experience-dependent visual cortex plasticity. At the level of synaptic transmission, activation of muscarinic receptors has been shown to play a permissive role in visual cortex plasticity. Among the muscarinic receptor subtypes, the M(1) receptor seems to make a predominant contribution towards modifications of neural circuitry. The signal transduction cascade of the cholinergic pathway may act synergistically with that of the NMDA receptor pathway, whose activation is a prerequisite for cortical plasticity.     

Ethical aspects of the safety of medicines and other social chemicals

The historical background of the discovery of adverse health effects of medicines, food additives, pesticides, and other chemicals is reviewed, and the development of national and international regulations and testing procedures to protect the public against the toxic effects of these drugs and chemicals is outlined. Ethical considerations of the safety evaluation of drugs and chemicals by human experimentation and animal toxicity studies, ethical problems associated with clinical trials, with the falsification of clinical and toxicological data, and with inadequate experimental methodology, are reviewed, and the ethics of the marketing of drugs and their post-marketing surveillance, are similarly considered. These ethical problems are illustrated with many specific examples, including the drugs neoarsphenamine, chloramphenicol, thalidomide, diethyl stilboestrol and benoxaprofen.     

Influence of handedness on spatial compatibility effects with perpendicular arrangement of stimuli and responses

The present study was conducted to determine a possible spatial compatibility effect in absence of any overt correspondence between spatial properties of stimuli and responses, in an experimental situation in which the stimuli were displayed vertically and the responding hands were disposed horizontally. The subjects were requested to make unimanual discriminative key-pressing responses to two light stimuli. The results indicate a preferential association of the dominant hand (right for right-handers and left for left-handers) with upper visual stimuli and the non-dominant hand with lower visual stimuli. This effect can result from a correspondence between the spatial codes associated with the location of the stimulus and the internal representation of the two hands along the vertical dimension, whereby the dominant hand is assigned a ‘higher’ position compared to the non-dominant hand. In this way the position of the two hands along the vertical dimension and the physical position of the two stimuli can be matched according to the same spatial code and producing the spatial compatibility effect reported in the present study.     

Genetics of neuronal migration in the cerebral cortex

The development of the cerebral cortex requires large-scale movement of neurons from areas of proliferation to areas of differentiation and adult function in the cortex proper, and the patterns of this neuronal migration are surprisingly complex. The migration of neurons is affected by several naturally occurring genetic defects in humans and mice; identification of the genes responsible for some of these conditions has recently yielded new insights into the mechanisms that regulate migration. Other key genes have been identified via the creation of induced mutations that can also cause dramatic disorders of neuronal migration. However, our understanding of the physiological and biochemical links between these genes is still relatively spotty. A number of molecules have also been studied in mice (Reelin, mDab1, and the VLDL and ApoE2 receptors) that appear to represent part of a coherent signaling pathway that regulates migration, because multiple genes cause an indistinguishable phenotype when mutated. On the other hand, two human genes that cause lissencephaly (LIS1, DCX) encode proteins that have recently been implicated as regulators or microtubule dynamics. This article reviews some of the mutant phenotypes in light of the mechanisms of neuronal migration. MRDD Research Reviews 6:34-40, 2000.     

Electrical potentials of the cerebral cortex and psychometric intelligence

Contradictory findings concerning relationships between intelligence-test scores and different EEG evoked-potential (EP) measures have been reported. The positive findings suggest that intelligence is correlated with the number and amplitude of components in the EP waveform. Since there is evidence that both of these parameters are influenced by stimulus intensity, we examined the extent to which an EP/intelligence relationship may depend on stimulus intensity. In a sample of 22 Ss a relationship between EP amplitude and intelligence was found and the magnitude of this correlation was related systematically to stimulus intensity. The maximum correlation (r = 0.69) with scores on the Raven's Advanced Progressive Matrices was obtained at an intermediate level of intensity. These findings may account for some of the inconsistencies in the literature. Moreover, they suggest an explanation for higher general intelligence in terms of greater central activation of neural processes in response to normal levels of stimulation.     

Opposing effects on muscarinic acetylcholine receptors in the piriform cortex of odor-trained rats

We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a phase of high capability to learn unfamiliar odors, using the same paradigm (“rule learning”). It has been reported that at 1–3 d after the acquisition of odor-discrimination rule learning, pyramidal neurons in the rat piriform cortex show enhanced excitability, due to a reduction in the spike-activated potassium current I_AHP, which is modulated by ACh. Further, ACh and its analog, carbachol (CCh), lost the ability to reduce the I_AHP in neurons from trained rats. Here we show that the reduced sensitivity to CCh in the piriform cortex results from a decrease in the number of mAChRs, as well as a reduction in the affinity of the receptors to CCh. Also, it has been reported that 3–8 d after the acquisition of odor-discrimination rule learning, synaptic transmission in the piriform cortex is enhanced, and paired-pulse facilitation (PPF) in response to twin stimulations is reduced. Here, intracellular recordings from pyramidal neurons show that CCh increases PPF in the piriform cortex from odor-trained rats more than in control rats, suggesting enhanced effect of ACh in inhibiting presynaptic glutamate release after odor training.     

The cognitive significance of resonating neurons in the cerebral cortex

Most neural fibers of the cerebral cortex engage in electric signaling, but one particular fiber, the apical dendrite of the pyramidal neuron, specializes in electric resonating. This dendrite extends upward from somas of pyramidal neurons, the most numerous neurons of the cortex. The apical dendrite is embedded in a recurrent corticothalamic circuit that induces surges of electric current to move repeatedly down the dendrite. Narrow bandwidths of surge frequency (resonating) enable cortical circuits to use specific carrier frequencies, which isolate the processing of those circuits from other circuits. Resonating greatly enhances the intensity and duration of electrical activity of a neuron over a narrow frequency range, which underlies attention in its various modes. Within the minicolumn, separation of the central resonating circuit from the surrounding signal processing network separates “having” subjective impressions from “thinking about” them. Resonating neurons in the insular cortex apparently underlie cognitive impressions of feelings.