Thalamic nuclei

The spontaneous electrical activity of the brain can be measured by electroencephalography (EEG), a technique that has been widely employed to study neurotoxic effects of chemicals both in humans and in experimental animals. EEG waves represent summated synaptic potentials generated by the pyramidal cells of the cerebral cortex (Misra 1992). These potentials are the responses of cortical cells to rhythmical changes arising from thalamic nuclei. The signals recorded can be separated into frequency bands—faster waves exceeding 13 Hz, and slower ones below 4 Hz. 

The precise role of melatonin in sleep and waking is uncertain but it seems to act as a go-between for the light and biological cycles and evidence suggests that it has a reciprocal relationship with the SCN (Fig. 22.3). Its actions are mediated by (MLi) receptors which are found predominantly in the SCN as well as thalamic nuclei and the anterior pituitary. These are G protein-coupled receptors, with seven transmembrane domains, that inhibit adenylyl cyclase. Their activation by melatonin, or an MLi agonist such as 2-iodomelatonin, restores the impaired circadian cycle in aged rats. 

Maintenance of these frequencies relies on the degree of depolarisation of the thalamic neurons (Jahnsen and Elinas 1985) and this, in turn, depends on the nature and intensity of their afferent inputs. The NspRTN and other thalamic nuclei receive reciprocal inputs from the cortex and it is possible that it is the ensuing oscillations in neuronal activity in this circuit between the cortex and thalamus that give rise to the sleep spindle waves in stages 2-4. In fact, it has been suggested that the stronger and clearer these oscillations become, the more likely it is that there will be loss of consciousness. 

Figure 22.5 Pathways involved in cortico-thalamic synchrony and EEG arousal. The ascending reticular activating system (ARAS) extends from the cephalic medulla through the pons and midbrain to the thalamus (see Moruzzi and Mayoun 1949). It is activated by impulses in collaterals of the spinothalamic sensory pathway running to specific thalamic nuclei (SpThNc) and in turn activates much of the cortex, partly through the non-specific thalamic nuclei (NspThNc), which also receive inputs from SpThNc and also via the nucleus basalis (NcB). Its stimulation is followed by EEG arousal. It is probable that reciprocal links between cortical areas and the thalamus, particularly NspThN, lead to slow-wave (8 Hz) cortical EEG synchrony and, in the absence of appropriate sensory input and ARAS activity, a sleep state...

Are released either in the cortex or the non-specific thalamic nuclei. 

The second cluster of neurons lies more caudally, near the pons, in the pedunculo-pontine (PPT) and laterodorsal tegmental (LDT) nuclei (see Fig. 22.6) and could be regarded as part of the ARAS (see McCormick 1992). It innervates the non-specific thalamic nuclei as well as some more specific ones like the lateral geniculate nucleus (visual pathway), the pontine reticular formation and occipital cortex. Because long... 

Administration of HA and its effect on sleep-wakefulness Local application of HA (5, 30 and 60 pg) in the TMN region of cats increased the latency to sleep, increased arousal, and reduced NREM sleep in a site-specific, dose-dependent manner. The highest dose produced the maximal effect, which lasted for 6 h. The HA-induced arousal was completely blocked when the cats were pretreated intraperitoneally with the Hi receptor antagonist mepyramine (Lin et at, 1986, 1988). In rats, intraventricular administration of HA blocked the increase in delta and theta activity (0-6 Hz) in the EEG induced by repeated low-frequency stimulation of the midbrain reticular formation. This effect was blocked if specific thalamic nuclei were lesioned (Tasaka et at, 1993) or by simultaneous administration of an Hi receptor antagonist, but not by an H2 receptor antagonist (Tasaka et at, 1989). Application of HA... 

Gonzalo-Ruiz, A., Lieberman, A R. Sanz-Anquela, J. M. (1995). Organization of serotoninergic projections from the raphe nuclei to the anterior thalamic nuclei in the rat a combined retrograde tracing and 5-HT immuno-histochemical study. J. Chem. Neuroanat. 8, 103-15. 

Neuropeptide S (NPS) is a recently discovered bioactive peptide that has emerged as a new signaling molecule in the complex circuitry that modulates sleep-wakefulness and anxiety-like behavior. The peptide precursor is expressed most prominently in a novel nucleus located in the perilocus coeruleus, a brain structure with well-defined functions in arousal, stress, and anxiety. NPS was also found to induce anxiolytic-like behavior in a battery of four different tests of innate responses to stress. Infusion of NPS potently increases wakefulness and suppresses non-REM (NREM) and REM sleep (Xu et al, 2004). NPS binds to a G-protein-coupled receptor, the NPS receptor, with nanomolar affinity activation of the receptor mobilizes intracellular calcium. The NPS receptor is expressed throughout the brain, particularly in regions relevant to the modulation of sleep and waking, in the tuberomammillary region, lateral hypothalamus, and medial thalamic nuclei. 

Due to its relevance to an understanding of movement disorders, the motor circuit has received the most attention. This circuit is centered on somatosensory, motor and premotor cortices, which send projections to the motor portions of striatum. The connections between the striatum and the basal ganglia output nuclei (GPi/SNr) are organized into direct and indirect pathways [1]. The direct pathway is a monosynaptic projection between striatum and GPi/ SNr, while the indirect pathway is a polysynaptic connection that involves intercalated neurons in GPe and STN. Some striatofugal neurons may also collateralize more extensively, reaching GPe, GPi/SNr and STN. Other motor -related inputs to striatum and STN arise from the intralaminar thalamic nuclei, i.e. the centromedian and parafascicular nuclei (CM/Pf). 

Thalamic nuclei Hypothalamus Corpus callosum Cerebellum (deep nuclear layer)... 

A global view of consciousness is that it is generated throughout the entire brain, as a result of synchronisation of relevant neural networks. Specific systems or regions—for example the cerebral cortex, brainstem reticular formation and thalamic nuclei—may be key anatomical integrators. Areas with the most widespread interconnections are pivotal, and on this basis the cortex and thalamus are more relevant than cerebellum and striatum for example. Frontal cortex for example connects with every other brain region, both in terms of input and output, with 80% of such connections accounted for by cortico-cortical connections. Thalamic intralaminar nuclei are, in conjunction with the reticular nucleus, reciprocally connected to all cortical areas. By contrast the cerebellum has very few output pathways and striatal-cortical input is (via the thalamus) confined to frontal lobe. 

Dopamine receptors include at least 4 subtypes which are concentrated in the striatum where D1 and D2 are evenly distributed and D3 is concentrated in the limbic portion, nucleus accumbens (Herroelen et al., 1994). D2 but not D1 receptors also occur throughout the cerebral cortex particularly temporal lobe, and D3 receptors are also present in lower densities in hippocampus and amygdala. D3 receptors are localised in several thalamic nuclei including the lateral geniculate, mediodorsal and anteroventral. 

Of the different sensory modalities, olfaction does not appear to feature in reports of the effects of plant hallucinogens. Since olfaction is the one sense not relayed through the thalamus, this brain area is likely to be central to the changes in consciousness described. Many target receptors implicated, e.g. muscarinic, 5-HT2, D2, D3 and opiate, are present in this thalamic nuclei the human brain. 

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