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What is Arousal?

▪ Arousal is a physiological and psychological state of being awake.▪ Arousal is nonuniform; we can be alert and attentive, or fail to notice what is going on around us.▪ Sleepiness has an effect on wakefulness: struggling to stay awake can affect our level of concentration▪ Five different neurotransmitters play a role in our level of arousal:- acetylcholine (ACh)- norepinephrine (NE)- serotonin (5-HT)- histamine- hypocretin


Neural Control of Arousal: Acetylcholine (ACh)

▪ Acetylcholinergic neurons are located in the dorsal pons, the basal forebrain and in the medial septum.▪ ACh antagonists and agonists decrease and increase cortical arousal, respectively (as measured by EEG activity).▪ ACh release in striatum, hippocampus and frontal cortex is associated with animals level of arousal (as measured by microdialysis).▪ Electrical stimulation of the dorsal pons region activates and stimulates ACh release in cerebral cortex. This can be be blocked by deactivating cholinergic neurons in the basal forebrain.Happen when awake and ASLEEP


Micro dialysis

Take samples of brain. Measure release of ach or other neurotransmitter.


Neural Control of Arousal: Norepinephrine (NE)

▪ NE neurons are located in Locus Coeruleus (LC).▪ NE neurons show an increase in firing rate when alert/awake and a decline in firing rate during sleep.▪ LC activity is related to vigilance - continuous attention.▪ Firing of LC neurons in monkeys is high during best performance. If the monkey has been working for a long time, performance declines and so does firing rate.widespread influence on brain. Decrease firing when asleep. Virtually zero during rem. All for lc neurons. Believe associate to vigilance. Continual monitoring of urroundings. SUSTAINED ATTENTION.


Neural Control of Arousal: Serotonin (5-HT)

▪ 5-HT (5-hydroxytryptamine) neurons are found in raphe nuclei.▪ Stimulation of raphe nuclei causes locomotion and cortical arousal (measured by EEG).▪ 5-HT neuron activation facilitates continuous movement.▪ 5-HT neuron activity declines when responding to novel stimuli (i.e. orienting your response).


Neural Control of Arousal: Histamine

▪ Histaminergic neurons are located in thetuberomammillary nucleus (TMN) of the hypothalamus.▪ Projections to basal forebrain influence ACh release in the cerebral cortex.▪ Histamine receptor blockers decrease waking and increase sleep.▪ Histaminergic neuron activity is high during waking and low duringsleep.▪ Histamine deprived mice fall asleep within a few minutes.Suppresses extraneous info when animal is focused on something. Aside on antihistamines and sleepiness, excep newer drugs. Histamine low during sleep of course


Neural Control of Arousal: Hypocretin

▪ Hypocretinergic neurons are located in the lateral hypothalamus.▪ The axons terminate in areas that are involved in arousal.▪ Hypocretinergic neurons fire at a high rate during awake and alert states, but fire at a low rate during slow wave sleep and REM, in anaesthetised animals.▪ Hypocretin plays a role in motor activity; high firing rates are observed when the animal is engaged in exploratory activity.▪ Narcolepsy is treated with a drug called modafinal, which stimulates hypocretin release in the thalamus. Cognitive enhancer? Amphetamines could be too and caffeine but addictive effects. Active waking, nremExploratory activity. Medafinol. Stimulant.


Raf important area of pons related to

Sleep neurotransmitterS


Neural Control of Sleep/Waking Behaviour

▪ The group of neurons in the preoptic area (located rostral to thehypothalamus) is involved in sleep behaviour.▪ Destruction of the preoptic area causes insomnia in rats.▪ In cats, sleep suppression eventually causes death.▪ Electrical stimulation of preoptic area causes drowsiness in cats and sometimes may cause immediate sleep.▪ Lesions of the ventrolateral preoptic area (VLPA) suppresses sleep.▪ VLPA neuron activity increases during sleep.▪ VLPA neurons contain inhibitory GABA secreting neurons which send their axons to the TMN, raphe nucleus and LC.Sleep suppression leads to intense firing of vlpa presumably in order to fall asleep


Sleep/waking flip-flop SEE TEXTBOOK!

The VLPA receives inhibitory inputsfrom the same regions it inhibits.▪ Reciprocal inhibition characterises a flip-flop circuit which assumes an ON or OFF state.▪ In the ON state, the arousal system (wake-promoting region) is active and the sleep-promoting region in the VLPA is inhibited (animal is awake).▪ In the OFF state, the sleep-promoting region in the VLPA is active and wake- promoting regions of the arousal system is inhibited (animal is asleep).▪ Neurons in both regions cannot be active at the same time.


Significance of sleep wake flip-flopremember this is hypothetical though!

▪ Switch from one state to another is fast; either asleep or awake.▪ Hypocretinergic neurons stabilise the flip-flop by promoting wakefulness and inhibiting sleep otherwise we would fall asleep during waking hours (i.e. keeps flip-flop in the ON state).


PGO Waves in REM Sleep

▪ Cerebral metabolism during REM sleep is as high as metabolism during waking hours.▪ PGO waves (pons, geniculate and occipital) are short electrical bursts that can only be measured in animals (invasive).▪ PGO waves originate in the pons and propagate to the LGN and then to the occipital (visual) cortex. Indicate first sign of rem sleep. Likeltpy due to dreaming. Neat chart showing go activity across sleep cycle for cat.


Neural Control of REM Sleep: ACh

▪ ACh agonists facilitate REM sleep.▪ ACh levels are high during waking hours and REM sleep and low during slow-wave sleep.▪ Acetylcholinergic neurons responsible for REM sleep are found in pedunculopontine nucleus (PPT) and the laterodorsal tegmental nucleus (LDT).▪ PPT and LDT are found within a region called the peribrachial area.


Firing Pattern of Acetylcholinergic REM-ON Neuron in Peribrachial Area

▪ Activity of single neuron in peribrachial area is related to sleep cycle.▪ REM-ON cells fire only during REM sleep.▪ The neuron increases its activity before the onset of REM sleep.▪ Lesions of the peribrachial area reduce REM sleep.▪ Neurons in the peribrachial area influence the thalamus, basal ganglia, the preoptic area, hippocampus, hypothalamus, cingulate cortex and brain stem nuclei that control eye movements.


Interaction between sleep/waking and REM Sleep flip-flop

▪ Sublaterodorsal nucleus (SLD) contains REM-ON neurons.▪ Ventrolateral periaqueductal gray matter (vlPAG) contains REM-OFF cells.▪ Stimulating REM-ON region elicits REM sleep. Inhibition disrupts it.▪ Stimulating REM-OFF region suppresses REM sleep. Inhibition increases it.


Circadian Rhythms and Zeitgebers

▪ The daily change in behaviour that follows a cycle of approximately 24 hours is known as a circadian rhythm.▪ Circadian rhythms are controlled by internal biological clocks.▪ Regular daily variation in the level of illumination normally keeps the clock adjusted to 24 hours. Light serves as Zeitgebers (“time giver”).▪ If animals are kept in constant darkness (or constant dim light), a brief period of bright light will reset their internal clock.


Rat activity during night-day cycle

▪ Rats are normally active at night.▪ If we shift the cycle by 6 hours, the rat’s activity cycle changes as well. That is, darkness occurs later and the body adapts to this change.


The Suprachiasmatic Nucleus (SCN)located in hypothalamus

▪ In rats , the internal biological clock is located in the suprachiastmatic nucleus (SCN) of the hypothalamus.▪ Lesions of the SCN disrupts the normal circadian rhythm of wheel running, drinking and hormonal secretions.▪ SCN lesions disrupt timing of sleep cycles but does not affect the total amount of sleep.SCN receives a direct projection of fibres from the retina (retinohypothalamic pathway) because light is the primary zeitgeber.


Changes in Circadian Rhythms

▪ Shift work or traveling across different time zones causes a dysnchronisation between the SCN controlled circadian rhythm and the external environment.▪ The disparity between internal rhythms and external environment leads to sleep disturbance, mood changes and affects normal functioning during waking hours.Aside on seasonal affect disorder. Require artificial light.