Sympathetic Fight or flight, preganglionc: in the intermediolateral column. Postganglionic: Sympathetic chain
blood vessels in skin and gut contract, rerouting blood to muscles
hairs stand on end, piloerection making us look more fearsome, bronchi dilate for incr oxygenation, heart rate accelerates. Sympathetic activity also stimulates adrenal medulla to relesase adrenaline and noradrenaline into the bloodstream to mobilize glucagon release from pancreas.
Parasympathetic: Preganglionic is in the brainstem, Peripheral ganglia in DRG
extrapyramidal system: is a neural network that is part of the motor system causing involuntary movements
pyramidal pathways (corticospinal and some corticobulbar tracts) may directly innervate motor neurons of the spinal cord or brainstem
extrapyramidal system centers on the modulation and regulation (indirect control)
Extrapyramidal tracts are chiefly found in the reticular formation of the pons and medulla, and target neurons in the spinal cord involved in reflexes, locomotion, complex movements, and postural control
* Hypothalamus as a critical center for coordination of both the autonomic and somatic components of emotional behavior
* Removed huge areas of the forebrain and noticed two basic types of behaviors
* One class exhibited as if they were enraged. Angry behavior occurred spontaneously and included the usual autonomic correlates of anger. Increased blood pressure and heart rate, dilation of pupil, hair raising. Also contained somatic motor components such as arching the back and tail. Called Sham rage
* Sham rage found to require the hypothalamus
* Stimulation of discreet parts of hypothalamus could elicit different behaviors associated with anger
## Hypothalamus as a coordinator of emotional behavior
* Phillip Bard / Walter Hess, early 1900s. Conducted seminal studies that determined the hypothalamus is a critical center for coordination of both the autonomic and somatic components of emotional behavior.
started by removing cerebral hemispheres of cats, when anesthesia wears off they acted as if enraged. Involved all the autonomic components of the sympathetic nervous system. Called sham rage because no obvious target.
Sham rage: Angry behavior occurred spontaneously included autonomic correlates of anger. Increased blood pressure and heart rate, dilation of pupil, hair raising. Also contained somatic motor components such as arching the back and tail.
Connection from ventral hypothalamus to midbrain needs to be present to elicit sham rage.
Bard suggested that emotional behaviors are often directed towards self-preservation (point also made by Charles Darwin).
* Both a volitional (with deliberate action) and a non-volitional component. Are in separate pathways. Both pathways ultimately lead to motor pools that activate muscle contraction or smooth muscle/gland secretions
* Lateral projections control specific movements or emotional behaviors, medial projections provide support for these behaviors
* Anatomists had shown that there was a subregion of the brain that formed a rim around the corpus callosum and the medial aspects of the cerebral hemispheres
* Contains the hippocampus and cingulate gyrus
* These areas found to form a circuit with other areas, including hypothalamus–amygdala, and parts of the thalamus. Together these areas make up the limbic system
Green is modern view of limbic system critical for processing emotion. Blue includes other areas of the traditional limbic system such as the hippocampus and mammillary bodies that are not considered critical to circuits for emotional processing.
* [Kluver-Bucy syndrome– a disease due to damage of temporal lobe and limbic system https://www.youtube.com/watch?v=7RDFRASiq4M](https://www.youtube.com/watch?v=7RDFRASiq4M)
* Cut out only 1 amygdala (remember there is one on each side of brain) at the same time as transecting the optic chiasm, corpus callosum and anterior commissure
* Optic chiasm cut blocks contralateral retinal axons thus now each eye’s information goes to same-side visual cortex
* Creates an animal with a single amygdala that had access only to visual inputs from the eye on the same side of the head
* If shut eye that goes to intact amygdala animals showed no fear responses. If open eye that maps to intact amygdala then animal shows normal fear behaviors. Therefore the amygdala is required for fear behaviors
patient SM has rare autosomal recessive condition called Urbach-Wiethe disease. Disorder of bilateral calcification an atrophy of anterior-medial temporal lobes. Both amygdalas are extensively damaged. Little to no injury of the hippocampus.
She has no motor or sensory or intelligence or memory or language impairment. However she can’t recognize the emotion of fear in photographs. Furthermore, she exhibits little fear herself (to dangerous animals, scary houses, films, etc).
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## Insights on the role of the amygdala in appraising emotions from patient S.M.
* Among 603 operations for control of untreatable aggressiveness...
* ...there were 481 cases with bilateral amygdalotomies and 122 cases with mostly secondary posteromedian hypothalamotomies that have been performed
* Initially excellent or moderate improvement was achieved in 76%. After a follow-up of more than three years this figure only slightly decreased to 70%. The group of patients who did not positively respond (30%) needs further study to discover the reasons for failure
* Pair a normally neutral stimulus with an inherently aversive one. Over time the animal will show behaviors to the neutral stimulus similar to that when given the aversive one. The animal learns to attach new meaning to a stimulus
* Can use this assay to determine what areas of the brain are required for the learned behavior
## Classic experiments demonstrating fear conditioning in an infant
A white rat presented to an infant does not innately elicit fear, but pairing the rat with an aversive noise, produces crying and attempts to crawl away, even when the rat was presented without the noise.
Classic experiments from Watson and Rayner demonstrating fear conditioning in an infant
As early as the 1920s, fear conditioning was demonstrated in infants. A white rat presented to an infant does not innately elicit fear, but pairing the rat with an aversive noise, produces crying and attempts to crawl away, even when the rat was presented without the noise.
CG– central gray or PAG (periaqueductal gray). Primary control center for descending pain modulation. Enkephalin releasing neurons that project to raphe nuclei (and 5-HT in turn excites inhibitory interneurons in the spinal cord dorsal horn). Role in analgesia and defensive behavior. Responsible for the ‘freezing’ behavior of conditioned fear, the arresting of somatomotor activity.
LH– lateral hypothalamus. Contains orexinergic neurons. Projects widely throughout nervous system. Promotes feeding behavior, arousal, reduces pain perception, regulates body temperature, digestive functions and blood pressure. Glutamate, endocannabinoids (anandamide), and orexin neuropeptides are main neurotransmitters in orexin neurons. Robust projections to posterior hypothalamus, tuberomammillary nucleus (histamine projection nucleus in posterior hypothalamus. Sole source of histamine pathways in human), arcuate nucleus (neuroendocrine neurons in mediobasal hypothalamus, prolactin, GHRH, ghrelin, neuropeptide-Y), paraventricular hypothalamic nucleus.
PVN– paraventricular nucleus of hypothalamus. Contains groups of neurons activated by stressful or other physiological changes. Release oxytocin or vasopressin into circulation through terminals in the pituitary.
Act at the level at the interface of the alpha and gamma subunits. Different neurons express different gamma subunits. Six different genes for the alpha subunit. Benzodiazepines only can interact with the a1,a2, and a5 subunits, have a conserved histidine.
* Emotional processing in the limbic system signals the presence or prospect for reward and punishment, and activates programs to procure rewards and avoid punishment
* Most known drugs (heroin, cocaine, ethanol, opiates, marijuana, nicotine, amphetamines) act on the limbic circuitry
* Most act by altering dopamine circuits that go through the basal ganglia
Much like the direct pathway. Inputs from different parts of cortex, including amygdala.
to MSNs in ventral striatum the nucleus accumbens. These gabaergic projections then inhibit inhibitory projections in the in the ventral globus pallidus called the ventral pallidum. So there is a disinhibitory effect, much as we discussed before for other basal ganglia loops.
- Neurons from ventral tegmental area (VTA) to nucleus accumbens (major neurotransmitter is dopamine)
- Critical pathway for drug addiction
5. VTA– nucleus accumbens pathway
- Acts as a rheostat of reward. Tells other brain centers how rewarding an activity is. The more rewarding an activity is deemed, the more likely the organism is to remember it well and repeat it
2. Amygdala:
- Helps assess whether an experience is pleasurable or aversive and whether it should be repeated or avoided to forge connections between an experience and other cues
3. Hippocampus:
- Recording the memories of an experience
4. Frontal regions:
- Coordinates and processes all this information and determines ultimate behavior of the individual
Specifically, studies in primates and rodents have shown that many VTA dopamine neurons encode reward prediction errors. This error signal is hypothesized to direct synaptic plasticity in target neurons in the nucleus accumbens and prefrontal cortex for reinforcement-based learning. If VTA dopamine neurons signal a reward, the action or behavior that immediately preceded the reward is reinforced through dopamine modulation of downstream circuits (see Figure 10–44). Drugs of abuse bypass natural signals that activate these dopamine neurons, thus dissociating the reward system from its natural stimuli. Specifically, by increasing dopamine concentration at dopamine neurons’ presynaptic terminals, drug consumption mimics dopamine neuron activation; this reinforces the preceding actions, include drug consumption itself. Thus, addictive drugs hijack the brain’s reward system and exploit mechanisms that otherwise regulate learning and motivational
<div><figcaption class="big">Synaptic locations of action for psychoactive drugs of abuse</figcaption><img src="figs/Neuroscience5e-Fig-29.11-1R_copy_9e75248.jpg" width="500px"><figcaption>Neuroscience 5e Fig. 29.11</figcaption></div>
<div><figcaption class="big">Functional changes at VTA projections in addicted individuals</figcaption><img src="figs/Neuroscience5e-Fig-29.11-2R_copy_d09517f.jpg" width="400px"><figcaption>Neuroscience 5e Fig. 29.11</figcaption></div>
Exposure to drugs of abuse causes long-lasting enhancement of excitatory input to VTA dopamine neurons, increasing AMPA/NMDA receptor ratio at these synapses.
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## Long-term changes in the brain as a result of abuse
* Decreases in CREB transcription factor in NAc (and extended amygdala)
* Decreases in metabolism in orbito frontal cortex (OFC)
* Social withdrawal, lack of motivation, cognitive impairment- Negative symptoms
* Chlorpromazine and reserpine are drugs that alleviate positive symptoms, with side effects
* Reserpine interferes with metabolism of all three monoamine neurotransmitters– dopamine, norepinephrine and serotonin by inhibiting a vesicular monoamine transporter (VMAT) effectively depletes the levels of these neurotransmitters
