48. Neuromodulatory CNS Centers

Question 1

Describe the imbalances seen in Alzheimer’s, Parkinson’s, Depression, Schizophrenia

What is Central Pontine Myelinolysis?

Answer 1

AD: lack of ACh in base of forebrain
PD: lack of DA in SN
D: lack of serotonin in brainstem
S: excess DA imbalance

CPM: “Locked-in” syndrome - loss of reticular activating axons - impaired consciousness, cognitive difficulties

Question 2

What are the 4 characteristics of neuromodulators?

Answer 2

1. SLOW (act through GPCRs - variety of actions)
2. Widely Varying types of NTs/substances
3. Effects AMPLIFIED (powerful/long lasting)
4. NON-SPECIFIC (less need for localization)

Question 3

What are the cell bodies and projections of DA, NE, ACh, and 5HT neurons in the CNS?

Answer 3

DA: midbrain (SN) -> basal ganglia, cerebrum
NE: pons -> brain, SC
ACh: basal forebrain -> cerebrum, autonomics
5HT: brainstem -> brain, SC

Question 4

How are catecholamines synthesized? How are their actions terminated?

Answer 4

1. Hydroxylation (Rate Limiting Step) - convert tyrosine to L-DOPA
2. Decarboxylation - convert L-DOPA to DA
3. hydroxylate DA to NE

Termination:
Primary- re-uptake: DAT, NET=UPTAKE1
Secondary- degradation: MAO, COMT

Question 5

What is the function of DA? Where is it released? What role does it play in a specific disease and how is it treated?

Answer 5

Released from SN to forebrain/limbic system
Major “reward” neuromodulator: learning how to get rewards, drug abuse
Sensory NT in visual/olfactory system

PD: degeneration of DA neurons in SNc (tx L-DOPA)

Question 6

What is the function of NE? Where is it released?

Answer 6

Fight/flight response
released throughout brian, SC
major arousal (wake vs sleep) released by Ascending Reticular Activating System

In most postganglionic neurons of sympathetic ANS

Question 7

How is serotonin synthesized? How is it terminated? what role does it play in disease and how is it treated? What is its function?

Answer 7

1. Hydroxylation (rate limiting step): Tryptophan to 5-HTP
2. Decarboxylation: 5-HTP to 5-HT

Termination: MAO degradation

Depression: due to low 5-ht, tx with SSRIs

Fx: arousal (with NE/ACh), homeostatic mechanisms, regulation of pain

Question 8

What is the function of Histamine? What is its function in the brain? What disease is associated with histamine?

Answer 8

H: released in brain as part of stress response, promotes arousal, high Histamine assoc with ANXIETY

From hypothalamus to forebrain/SC, stimulate ACh nuclei

Question 9

What are the higher level functions of ACh? How to treat diseases assoc with ACh?

Answer 9

maintain cerebral cortex fx through arousal
AD: loss of ACh, tx with antiChE - limited effectiveness
Involved in wake/sleep cycle (high during wake/REM, low during slow wave)

Question 10

What are the locations of cell bodies for DA, NE, 5HT, H, and ACh?

Answer 10

DA: SNc and ventral tegmental areas (MIDBRAIN)
NE: Locus Ceruleus (Pons)
5HT: Raphe Nuclei (Dorsal Raphe Nuclei in Pons, others in midbrain/medulla)
H: Tuberomammilary Nucleus of HYPOTHALAMUS
ACh: Basal nucleus of forebrain, Substantia innominata (anterior perforated substance) (BASAL FOREBRAIN)

Question 11

What are the functions of D1/D2 receptors? How does PD work? Where is this?

Answer 11

Receptors in Striatum (Putamen)
D1: stimulating, DIRECT pathway to initiate movement
D2: inhibiting, INDIRECT pathway to block movement

DA: stim D1 and inhibit D2 to initiate movment
PD: less DA - no D1 stim and no block of D2 = inhibited movement

Question 12

What are the broad functions of NE, ACh, 5HT, DA, H? What NTs are active during non-REM sleep?

What happens if your body does not have enough Orexin?

Answer 12

NE: arousal, action (fight/flight)
ACh: ANS control, movement, cognitive fx, attention, REM SLEEP
5HT: mood, pain relief
DA: reward, learning, movement
H: anxiety, pain

NonREM: GABA, Galanin

Orexin: peptide NT to arousal centers (less orexin = NARCOLEPSY)