Wakefulness cortical activation

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With this in mind, the search for molecular markers that define populations of neurons in areas important for arousal is clearly warranted. In this chapter we describe the identification of four peptidergic systems that modulate different aspects of the sleep-wakefulness cycle. The success of this strategy demonstrates the need for new markers of neuronal cell types, which may define populations of neurons critical for our understanding of cortical activity and sleep. 

We do not yet know if the left-right differences in cortical activation (measured in the waking EEG by Davidson) will persist, or be nullified, or even reversed in REM sleep, but we do know that compared to waking, the amygdala and its directly adjacent cortical areas, the parahippocampal and anterior cingulate regions, are selectively activated in REM sleep and, as discussed in the previous section, that this preferential limbic activation is reciprocal to deactivation of both dorsolateral prefrontal cortices. 

We were further interested in the potential EEG cortical activation and cognitive properties of GT-2016. EEG studies confirmed the unique wake-promoting or vigilant properties of GT-2016.76 Subsequently, we conducted studies in collaboration with Dr. James McGaugh at the Univ. of California, Irvine to establish... 

The more synchronised the activity of the cortical neurons, the greater the summation of currents and the larger and slower the EEG wave, as in the sleep pattern (Fig. 22.4). While there are some dissociations between EEG pattern and behavioural states, the EEG offers one way of determining experimentally the pathways (and neurotransmitters) that control arousal and sleep, and can be regarded as an important objective measurement of the cortical correlates of sleep and waking. 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

ACh regulates the cortical arousal characteristic of both REM sleep and wakefulness (Semba, 1991, 2000 Sarter Bruno, 1997, 2000). Medial regions of the pontine reticular formation (Figs. 5.2 and 5.7) contribute to regulating both the state of REM sleep and the trait of EEG activation. Within the medial pontine reticular formation, presynaptic cholinergic terminals (Fig. 5.1) that release ACh also are endowed with muscarinic cholinergic receptors (Roth et al, 1996). Autoreceptors are defined as presynaptic receptors that bind the neurotransmitter that is released from the presynaptic terminal (Kalsner, 1990). Autoreceptors provide feedback modulation of transmitter release. Autoreceptor activation... 

The basal forebrain is an important way station in the activation of the cerebral cortex from the reticular activating system. AMPA and NMDA injections into the basal forebrain increase wakefulness and reduce sleep (Cape Jones, 2000 Manfridi et al, 1999), effects that are blocked by AMPA and NMDA receptor antagonists (Manfridi et al, 1999). The excitatory cortical projections of the basal forebrain have long been considered purely cholinergic, but many basal forebrain neurons that project to the cortex are now known to contain Glu, which may function as a co-transmitter or even as the primary excitatory neurotransmitter (Manns et al, 2001). The basal forebrain also affects vigilance via synapses to HCT cells in the lateral hypothalamus some of these synapses are glutamatergic (Henny Jones, 2006). 

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