Exam 2: Brainstem Consciousness and Neurotransmitters

Question 1

Locked in syndrome

Answer 1

damage to the corticospinal tract (usually) that incapacitates movement but not sensation or consciousness. Eye movement is spared so that is the only method of communication

Question 2

where/what is the reticular formation

Answer 2

Within the brainstem, there are groups of nuclei that run the length of the brainstem, called the reticular formation. These nuclei will send their axons diffusely all over the cortex.

Question 3

Rostral reticular formation function and location

Answer 3

The rostral reticular formation is critical for arousal and consciousness
This group of nuclei are in the midbrain and upper pons

Question 4

Caudal reticular formation

Answer 4

The caudal reticular formation is critical for motor, reflex and autonomic functions
This group of nuclei are in the pons and medulla

Question 5

Consciousness requires cortical and subcortical networks of neurons with the (2)

Answer 5

frontoparietal association cortex and arousal circuits in the reticular formation

Question 6

Levels of consciousness

Answer 6

1. Alertness (arousal) – dependent on rostral reticular formation
2. Attention – dependent on rostral reticular formation and frontroparietal regions
3. Awareness – summarizing the sensory, motor, emotional and memory information into a subjective personal experience

Question 7

What does damage to rostral but not caudal do?

Answer 7

eliminates arousal

Question 8

What can stimulations of the rostral reticular formation do?

Answer 8

arouse someone out of deep anesthesia

Question 9

How does the reticular formation actually regulate arousal?

Answer 9

Via projections to the thalamus, hypothalamus and basal forebrain

Question 10

The neurotransmitters involved fall under two categories:

Answer 10

1) Fast acting excitatory or inhibitory, generally involving glutamate and GABA
2) Slow acting, modulatory involving dopamine, acetylcholine, and norepinephrine

Question 11

WHich areas have GLutamate and GABA and which areas have neuromodulatory neurotransmitters

Answer 11

Intrinsic cortical neurons, such as the pyramidal cells, generally have glutamate or GABA as their neurotransmitters. The projection systems and subcortical system are what will contain the neuromodulatory neurotransmitters.

Question 12

Rostral reticular (function, location, projections, neurotransmitter, damage)

Answer 12

• Function: Alertness (most direct)
• Location of nuclei: rostral pons and midbrain (rostral reticular formation)
• Where it projects to: thalamic intralaminar nuclei, hypothalamus and basal forebrain
• The intralaminar nuclei have diffuse projections to the cortex
• Neurotransmitter used: glutamate in some neurons but otherwise unknown
• Damage: can cause coma

Question 13

Brain death (function lost, function maintained, causes, diagnose)

Answer 13

• Function lost: Occurs when there is no function in the forebrain or brainstem
• Function maintained: There might be spinal cord reflexive function still maintained
• Causes: heart attack, massive injuries to the brain, death. This is a permanent lack of brain activity.
• How to diagnose: lack of activity in forebrain/brainstem, no brainstem reflexes, no breathing

Question 14

Coma (function lost, function maintained, causes, diagnose)

Answer 14

• Function lost: impaired function of the cerebral cortex and rostral reticular formation and no sleep-wake cycles
• Function maintained: brainstem and spinal cord reflezes, activity in the cerebral cortex (though it is abnormal)
• Causes: Trauma or lack of oxygen. This is generally a temporary condition
• How to diagnose: lack of purposeful responses, minimal brain activity but maintained reflexes

Question 15

Vegetative state (function lost, function maintained, causes, diagnose)

Answer 15

• Some individuals who are in a coma enter a state where they regain some limited function, though are still not “conscious” fully
• In their case, the individuals regain some rostral reticular system activation and sleep wake cycles
• The cerebral cortex is still in a “coma” state

Question 16

Minimally conscious state (function lost, function maintained, causes, diagnose)

Answer 16

(function lost, function maintained, causes, diagnose)

Question 17

Acetylcholine (function, location, projections, neurotransmitter, damage)

Answer 17

• Function: alertness, memory and some locomotor function
• Location of nuclei:
  Basal forebrain (main source) – subcortical region
  Pontomesencephalic region, between the pons and midbrain
• Where it projects to:
  1. Cerebral cortex (memory)– projections to the hippocampus produce a rhythmic firing that is thought to aid in memory formation
  2. Thalamus (alertness), cerebellum (motor), pons/medulla (motor)
• Neurotransmitter used:
  Acetylcholine, with both muscarinic and nicotinic receptors
• Damage: problems with memory and drowsiness. Memory problems in Alzheimer’s stem from basal forebrain death

Question 18

Dopamine (function, location, projections, neurotransmitter, damage)

Answer 18

• Function: movement, working memory, initiative
• Location of nuclei:
  Midbrain – ventral tegmental area (VTA) and substantia niagra
• Where it projects to:
  Mesostriatal (aka nigrostriatal) – substantia niagra to striatum (subcortical), for movement
  Mesolimbic – VTA to nucleus accumbens and other limbic structures (subcortical), for reward and addiction
  Mesocortical – VTA to prefrontal cortex (cortical), for working memory and movement initiation
• Neurotransmitter used:
  Dopamine – metabotropic receptors
• Damage:
  Mesostriatal – movement disorders such as Parkinson’s
  Mesolimbic – overactivity leads to addiction, and to positive symptoms seen on schizophrenia
  Mesocortical – negative symptoms with schizophrenia and working memory deficits with Parkinson’s

Question 19

Norepinephrine (function, location, projections, neurotransmitter, damage)

Answer 19

• Function: alertness, mood and sleep-wake states
• Location of nuclei:
  Pons – locus coeruleus, are highly active during awake periods
  Pons/medulla - lateral tegmental area, have sympathetic functions such as blood pressure control
• Where it projects to:
  Entire cerebral cortex, including the cerebellum, brainstem, and spinal cord
• Neurotransmitter used:
  Norepinephrine – generally excitatory but inhibitory to the thalamus
• Damage:
  ADHD medications often target the NE system
  Narcolepsy medications target the NW system

Question 20

Serotonin (function, location, projections, neurotransmitter, damage)

Answer 20

• Function: Alertness, mood elevation, pain control, breathing control
• Location of nuclei:
  Raphe nuclei throughout the midbrain, pons and medulla
• Where it projects to:
  Entire CNS:
  To spinal cord and medulla for pain and motor control
• Neurotransmitter used:
  Serotonin – both excitatory and inhibitory effects
• Damage:
  1. Depression, anxiety disorders, OCD all have a serotonin dysfunction
  2. Sudden infant death syndrome (SIDS) is thought to involve defects in the 5HT system

Question 21

Stages 1-4 of sleep/wake cycles

Answer 21

1. Medulla
2. Ventral preoptic area (VLPO) of the anterior hypothalamus
   a. GABAergic neurons in this area send their axons to the brainstem arousal system and inhibit them. This inhibits the ascending projection pathways of the brainstem, preventing arousal and promoting sleep.
3. Posterior hypothalamus
   a. Hypocretin neurons in the this region excite the brainstem pathways, promoting arousal (these get inhibited)
   b. In narcolepsy, there is a loss of hypocretin neurons that promotes the transition to REM sleep.
4. Basal forebrain

Question 22

REM sleep sleep/wake cycles

Answer 22

1. Pontine reticular formation and VLPO
   a. GABAeric neurons in this region inhibit specific widespread systems important for arousal, promoting sleep
   b. Certain wide spread systems are disinhibited including the norepinephrine system from the ventral tegmental area in the midbrain and serotonin system in the raphe nucleus.
   c. This gives the appearance of arousal and an “alert” active brain
2. During REM sleep, there is active inhibition of lower motor neurons in the brainstem and spinal cord mediated by glycine, which prevents motor movements during sleep.

Question 23

Narcolepsy background + symptoms

Answer 23

1. Narcolepsy is chronic disorder that typically has an onset in adolescence or early adulthood
2. Symptoms: excessive daytime sleepiness, sudden loss of muscle tone (cataplexy) evoked by strong emotion, sleep paralysis, hallucinations (while falling asleep and waking up)

Question 24

Narcolepsy subtypes:

Answer 24

1. NT1=presence of cataplexy and low hypocretin levels

2. NT2=no cataplexy and normal hypocretin levels

Question 25

Narcolepsy

Answer 25

NT1 pathology:

a. Autoimmunity – antigen presenting pathway dysregulation is seen in those with NT1
b. Infection – “H1N1 influenza A virus infections and a peak in NT1 incidence 3–6 months later” reported in study from China during the 2009-2010 flu season
c. Hypocretin deficiency – hypocretin levels are severely decreased, possibly due to autoimmune processes
1) So what does a lack of hypocretin do? Patients have a harder time maintaining vigilance during wake states, which creates a lower threshold to fall asleep. Essentially, patients transitions between excessive sleepiness and sleep.
2) Patients with NT1 transition quicker from NREM to REM sleep, and also are more likely to have REM sleep disorders

Question 26

Narcolepsy Treatments

Answer 26

1) Psychostimulants
a. These medications help stimulate arousal, and can include drugs like Ritalin and Provigil. Stimulants typically increase DA levels (by blocking reuptake most commonly), and this helps stimulate hypothalamic structures important for arousal
b. Side effects: headache, nausea, potential sympathetic activity
2) Antidepressants
a. SSRIs and SNRIs (selective 5HT and NE reuptake inhibitors) tend to suppress REM sleep and promote arousal
3) Xyrem
a. Works as a CNS depressant, possibly through GABA channel activation and can promote nighttime sleep as result
b. Side effects: nausea, sleepwalking issues, and breathing issues if taken with other sleep medications