View source for Vibrissal thalamic modes

===Neuromodulators set network modes===
Neurotransmitters often act through ionotropic receptors (ligand-gated channels), while neuromodulators act through metabotropic receptors (G-protein coupled).  The effects of neurotransmitters acting on ionotropic receptors are usually phasic, lasting only 10’s of milliseconds.  The effects of neuromodulators acting on metabotropic receptors are usually slower and longer lasting, in the range of 100's of milliseconds to seconds or more. However, the distinction between a neurotransmitter and a neuromodulator can be rather arbitrary and most neuroactive substances can function as both. For instance, a substance acting as a neuromodulator can alter the properties of ion channels that are activated by the same substance acting as a neurotransmitter (e.g. by affecting channel opening probabilities, receptor desensitization, release).  Substances acting on ionotropic receptors may also (appear to) act as neuromodulators if the presynaptic neuron fires continuously in a sustained manner.    

A number of substances are well-known neuromodulators and some of these have significant actions in the thalamocortical network:

- '''Glutamate''' acts on ionotropic receptors (AMPA, NMDA, kainate) and on metabotropic receptors (mGluR1-8).  Glutamate is released by lemniscal and corticothalamic synapses. It appears that metabotropic receptors are selectively activated by corticothalamic synapses innervating NRT and thalamocortical cells (McCormick and von Krosigk, 1992), and not by lemniscal synapses (Castro-Alamancos, 2002a).  

- '''GABA''' acts on ionotropic receptors (GABA<sub>A</sub>) and metabotropic receptors (GABA<sub>B</sub>). GABA is released by NRT cells. 

- '''Norepinephrine''' is a catecholamine acting on α and β type metabotropic receptors.  Noradrenergic neurons are found in the locus coeruleus in the brainstem reticular formation, from where they project throughout the brain, including the thalamus. Noradrenergic neurons discharge robustly during high levels of vigilance and attention, reduce their firing during slow-wave sleep and stop firing during paradoxical (also called, “rapid eye movement”; REM ) sleep (Foote et al., 1980).

- '''Dopamine''' is a catecholamine acting on D1 and D2 type metabotropic receptors. So far, there is little evidence of any role of dopamine in the vibrissa thalamocortical network. 

- '''Histamine''' acts on H<sub>1</sub>-H<sub>4</sub> type metabotropic receptors. Histamine neurons are found in the posterior hypothalamus, in the tuberomammillary complex, from where they project throughout the brain, including the thalamus. Histaminergic neurons discharge robustly during wakefulness (Brown et al., 2001). 

- '''Serotonin''' acts on ionotropic (5-HT<sub>3</sub>) and metabotropic (5-HT<sub>1</sub>, 5-HT<sub>2</sub> 5-HT<sub>4</sub>, 5-HT<sub>5</sub>, 5-HT<sub>6</sub>, 5-HT<sub>7</sub>) receptors. Serotonin neurons are found in the raphe nuclei in the brainstem reticular formation, from where they project throughout the brain, including the thalamus. Similar to noradrenergic neurons, 5-HT neurons fire tonically during wakefulness, decrease their activity in slow-wave sleep, and are nearly quiet during paradoxical sleep (McGinty and Harper, 1976; Trulson and Jacobs, 1979). 

- '''Acetylcholine''' acts on ionotropic (nicotinic) and metabotropic (muscarinic) receptors. Acetylcholine neurons projecting to the thalamus are found in the pedunculopontine nuclei (PPT) and in the dorsolateral tegmental nuclei (LDT) in the brainstem. Acetylcholine neurons are also found in the basal forebrain from where they project to the neocortex.  Cholinergic neurons in the LDT/PPT complex discharge vigorously during paradoxical sleep and also during wakefulness (el Mansari et al., 1989), and the levels of acetylcholine increase in the thalamus during those states (Williams et al., 1994).

- '''Neuropeptides''' usually act at metabotropic receptors. Neurons very often make both a conventional neurotransmitter (glutamate, GABA) and one or more neuropeptides. Examples include opioids (endorphins, enkephalins, dynorphins), substance P, etc. 

- '''Hormones''' are chemicals released by cells that affect cells in other parts of the organism generally through the bloodstream. For example, epinephrine (adrenaline) is a catecholamine that is released by the adrenal gland. 

- Other '''intrinsic neuroactive substances''' released within the thalamus may include adenosine, cannabinoids, growth factors, cytokines, etc. 

- '''Extrinsic neuroactive substances''' that reach the thalamus may also affect thalamic modes. For example, nicotine from tobacco, caffeine from coffee, etc.