12+Anatomy+and+Physiology

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=Braindevelopment=

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[|Hans Berger], the inventor of the [|electroencephalogram] was the first to propose the idea that the brain is constantly busy. In a series of papers published in 1929 he showed that the electrical oscillations detected by his device do not cease even when the subject is at rest. However his ideas were not taken seriously and a general perception formed among neurologists that only when a focused activity is performed does the brain (or a part of the brain) becomes active.[|[10]] Later, experiments by the group of neurologist Marcus E. Raichle's at [|Washington University School of Medicine] and other groups showed that the brain's energy consumption is increased by less than 5% of its baseline energy consumption while performing a focused mental task. These experiments showed that the brain is constantly active with a high level of activity even when the person is not engaged in focused mental work. Research thereafter focused on finding the regions responsible for this constant background activity level.[|[10]] Raichle coined the term "default mode" in 2001 to describe resting state brain function;[|[11]] the concept rapidly became a central theme in [|neuroscience].[|[12]] The brain has other Low Frequency Resting State Networks (LFRSNs), such as visual and auditory networks.[|[2]]

=Serotonin= Serotonin is a neurotransmitter, and is found in all [|bilateral animals], where it mediates gut movements and the animal's perception of resource availability. In the simplest animals, resources are equivalent with food, but in advanced animals such as [|arthropods] and [|vertebrates], resources also can mean social dominance. In response to the perceived abundance or scarcity of resources, the animal's growth, reproduction or [|mood] may be elevated or lowered. Recent studies involving the serotonin transporter gene 5-HTT have shown the short allele of this gene increases synaptic serotonin levels. These genetic studies have demonstrated serotonin has strong associations with depression in regards to a negative environment.

Gross anatomy
The neurons of the [|raphe nuclei] are the principal source of 5-HT release in the brain.[|[57]] The raphe nuclei are neurons grouped into about nine pairs and distributed along the entire length of the [|brainstem], centered around the [|reticular formation].[|[58]] Axons from the neurons of the raphe nuclei form a [|neurotransmitter system], reaching almost every part of the central nervous system. Axons of neurons in the lower [|raphe nuclei] terminate in the [|cerebellum] and [|spinal cord], while the axons of the higher nuclei spread out in the entire brain.

Microanatomy
Serotonin is released into the space between neurons, and diffuses over a relatively wide gap (>20 µm) to activate [|5-HT receptors] located on the [|dendrites], cell bodies and [|presynaptic terminals] of adjacent neurons.

Receptors
Main article: [|5-HT receptor] The [|5-HT receptors] are the [|receptors] for serotonin. They are located on the cell membrane of [|nerve cells] and other cell types in animals, and mediate the effects of serotonin as the [|endogenous] [|ligand] and of a broad range of pharmaceutical and [|hallucinogenic drugs]. With the exception of the [|5-HT3 receptor], a ligand-gated [|ion channel], all other 5-HT receptors are [|G protein-coupled, seven transmembrane] (or //heptahelical//) receptors that activate an [|intracellular] [|second messenger] cascade.[|[59]]

Termination
Serotonergic action is terminated primarily via [|uptake] of 5-HT from the synapse. This is accomplished through the specific [|monoamine transporter] for 5-HT, [|SERT], on the presynaptic neuron. Various agents can inhibit 5-HT reuptake, including [|MDMA] (ecstasy), [|amphetamine], [|cocaine], [|dextromethorphan] (an [|antitussive]), [|tricyclic antidepressants] (TCAs) and [|selective serotonin reuptake inhibitors] (SSRIs). Interestingly, a 2006 study conducted by the [|University of Washington] suggested a newly discovered monoamine transporter, known as [|PMAT], may account for "a significant percentage of 5-HT clearance".[|[24]] Contrasting with the high-affinity SERT, the PMAT has been identified as a low-affinity transporter, with an apparent Km of 114 micromoles/L for serotonin; approximately 230 times higher than that of SERT. However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport //capacity// than SERT, "..resulting in roughly comparable uptake efficiencies to SERT in heterologous expression systems." The study also suggests some SSRIs, such as [|fluoxetine] and [|sertraline], inhibit PMAT but at [|IC50] values which surpass the therapeutic plasma concentrations by up to four orders of magnitude; therefore, SSRI monotherapy is //ineffective// in PMAT inhibition. At present, there are no known pharmaceuticals which would appreciably inhibit PMAT at normal therapeutic doses. The PMAT also suggestively transports dopamine and norepinephrine, albeit at Km values even higher than that of 5-HT (330–15,000 μmoles/L).

Serotonylation
Main article: [|Serotonylation] Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins.[|[32]] This process underlies serotonin effects upon platelet-forming cells ([|thrombocytes]) in which it links to the modification of signaling enzymes called [|GTPases] that then trigger the release of vesicle contents by [|exocytosis].[|[60]] A similar process underlies the pancreatic release of insulin.[|[32]] The effects of serotonin upon vascular smooth muscle "tone" (this is the biological function from which serotonin originally got its name) depend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.[|[61]]

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=Frontal Lobe=

Forebrain asymmetry of emotion
There are two sides of the brain, and so if there are separate time-based representations of the sentient self that subserve awareness in the anterior insular cortex (AIC) (one in each side), how are they coordinated to generate one unified self? The homeostatic model of awareness presented in this and prior articles1,78 suggests that there is an energy efficiency-optimal process that is based on the coordinated opponency of the autonomic system — that activity in the right side of the forebrain is associated with energy expenditure, sympathetic activity, arousal, withdrawal (aversive) behaviour and individual-oriented (survival) emotions, and activity in the left side is associated with energy nourishment, parasympathetic activity, relaxation, approach (appetitive) behaviour and group-oriented (affiliative) emotions. This proposal is described in detail in prior articles78,95. Briefly, the origin of this asymmetry can be related to the asymmetric autonomic innervation of the heart, and its evolutionary development would have been compelled by the need for energy optimization in the brain (which consumes 25% of the body’s energy). This model fits with an accumulating body of psychophysical literature which indicates that the left and right forebrain halves are differentially associated with positive and negative affect96 and, importantly, with the anatomical and functional asymmetry in the homeostatic afferent input to the insular cortex5,97,98 and in forebrain cardiac control99. It can explain why under particular conditions the AIC is more active on one side (FIG. 2) but also why in most conditions the two sides display joint activity, which mirrors the coordinated sympathetic and parasympathetic control of the heart. The model offers explanations for why positive emotions can reduce or block negative emotions (and vice versa), why the left (affiliative, vagal) side controls deictic pointing and verbal communication, and how increased parasympathetic activity (for example, activation of vagal afferents by gastric distension, slow breathing or elecrical stimulation) can reduce negative emotions (for example, pain). Given the many asymmetries in the activations of the AIC noted in this article, investigations addressing this model in split-brain patients could be enlightening, particularly if performed with those rare patients in whom boththe corpus callosum and the anterior commissure are sectioned100,101.

=Mirror Neuron= A **mirror neuron** is a [|neuron] that [|fires] both when an animal acts and when the animal observes the same action performed by another.[|[1]][|[2]] Thus, the neuron "mirrors" the behavior of the other, as though the observer were itself acting. Such neurons have been directly observed in [|primate] and other species including [|birds]. In humans, brain activity consistent with that of mirror neurons has been found in the [|premotor cortex], the [|supplementary motor area], the [|primary somatosensory cortex] and the [|inferior parietal cortex]. Some scientists consider mirror neurons one of the most important recent discoveries in [|neuroscience]. Among them is [|V.S. Ramachandran], who believes they might be very important in [|imitation] and [|language acquisition].[|[3]] However, despite the excitement generated by these findings, to date no widely accepted neural or [|computational models] have been put forward to describe how mirror neuron activity supports cognitive functions such as imitation.[|[4]] The function of the mirror system is a subject of much speculation. Many researchers in cognitive neuroscience and cognitive psychology consider that this system provides the physiological mechanism for the perception action coupling (see the [|common coding theory]). These mirror neurons may be important for understanding the actions of other people, and for learning new skills by imitation. Some researchers also speculate that mirror systems may simulate observed actions, and thus contribute to [|theory of mind] skills,[|[5]][|[6]] while others relate mirror neurons to [|language] abilities.[|[7]] It has also been proposed that problems with the mirror system may underlie cognitive disorders, particularly [|autism].[|[8]][|[9]] However the connection between mirror neuron dysfunction and autism is tentative and it remains to be seen how mirror neurons may be related to many of the important characteristics of autism.[|[4]] In the 1980s and 1990s, [|Giacomo Rizzolatti] was working with Giuseppe Di Pellegrino, [|Luciano Fadiga], Leonardo Fogassi, and [|Vittorio Gallese] at the [|University of Parma], [|Italy]. These neurophysiologists had placed [|electrodes] in the ventral premotor cortex of the [|macaque] monkey to study [|neurons] specialized for the control of hand and mouth actions; for example, taking hold of an object and manipulating it. During each experiment, they recorded from a single neuron in the monkey's brain while the monkey was allowed to reach for pieces of food, so the researchers could measure the neuron's response to certain movements.[|[10]][|[11]] The discovery was initially sent to [|Nature] but was rejected for its “lack of general interest”.[|[12]] They found that some of the neurons they recorded from would respond when the monkey saw a person pick up a piece of food as well as when the monkey picked up the food. A few years later, the same group published another empirical paper and discussed the role of the mirror neuron system in action recognition, and proposed that the human [|Broca’s region] was the [|homologue] region of the monkey ventral premotor cortex.[|[13]] Further experiments confirmed that about 10% of neurons in the monkey inferior frontal and inferior parietal cortex have 'mirror' properties and give similar responses to performed hand actions and observed actions. More recently Christian Keysers and colleagues have shown that, in both humans and monkeys, the mirror system also responds to the sound of actions.[|[14]][|[15]] Reports on mirror neurons have been widely published[|[16]] and confirmed[|[17]] with mirror neurons found in both inferior frontal and inferior parietal regions of the brain. Recently, evidence from [|functional neuroimaging] strongly suggests that humans have similar mirror neurons systems: researchers have identified brain regions which respond during both action and observation of action. Not surprisingly, these brain regions include those found in the macaque monkey.[|[1]] However, [|functional magnetic resonance imaging] (fMRI) can examine the entire brain at once and suggests that a much wider network of brain areas shows mirror properties in humans than previously thought. These additional areas include the [|somatosensory cortex] and are thought to make the observer feel what it feels like to move in the observed way [|[18]][|[19]]