Chemically Defined Circuits

Question 1

2 main sources of NEUROMODULATORY acetylcholine in CNS:

Answer 1

• pedunculopontine tegmental nuclei (lateral reticular formation)
• laterosdorsal tegmental nuclei (PAG, between midbrain and pons)

Project to thalamus, then cortex

Question 2

Role of neuromodulatory acetylcholine?

Answer 2

Arousal, locomotor movements

Question 3

Direct cholinergic input to cortex is from the ______

Answer 3

Nucleus basalis of Meynert

Question 4

Direct cholinergic input to cortex is from the ______

Answer 4

• Medial septal nuclei

- Nucleus of the diagonal band

Question 5

MAIN functions of acetylcholine in the CNS:

Answer 5

Attention, memory, learning

Blockage leads to delirium and memory deficits

Question 6

Dopamine is found mainly in the ventral midbrain in…

Answer 6

• Substantia nigra pars compacta
• Ventral tegmental area

Cognitive, motor, neuroendocrine functions

Question 7

3 projection systems of dopamine?

Answer 7

• Mesostriatal (from pars compacta; project to caudate and putamen)
• Mesolimbic (from ventral tegmental area; project to limbic structures - medial temporal cortex, amygdala, cingulate gyrus, nucleus accumbens)
• Mesocortical (from ventral tegmental area; project to prefrontal cortex)

Question 8

Dysfunction of mesostriatal pathway leads to…

Answer 8

Parkinson’s (treat with dopaminergic agonists)

Question 9

Overactivity of mesolimbic pathway leads to…

Answer 9

“Positive” symptoms of schizophrenia (hallucinations)

Often respond to dopaminergic agonists

Question 10

Dysfunction of mesocortical pathway leads to…

Answer 10

Cognitive deficits and hypokinesia in Parkinson’s

“Negative” symptoms of schizophrenia

Question 11

Norepinephrine comes from…

Answer 11

• Nucleus ceruleus
• Scattered nuclei in lateral tegmental area

Ascending projections reach entire forebrain
(also to cerebellum, brainstem, spinal cord)

Question 12

Norepinephrine is both inhibitory and excitatory, but is mainly excitatory to the _______.

Functions include:

Answer 12

Thalamus

• Modulation of attention
• Sleep-wake states (locus ceruleus activity higher in wake)
• Mood

Question 13

Norepinephrine-enhancing medications can treat…

Answer 13

• ADD

- Narcolepsy

Question 14

Norepinephrine and serotonin together are important in…

Answer 14

Mood disorders (depression, manic-depressive)
Anxiety disorders (OCD)

Question 15

Serotonin is found in…

Answer 15

Raphe nuclei in midbrain, pons, and medulla

• Rostral projects to forebrain (cortex, thalamus, basal ganglia)
• Caudal projects to cerebellum, medulla, spinal cord

**Also in some regions like area postrema and caudal locus ceruleus

Question 16

Rostral serotonin projections play a role in:

Caudal projections play a role in:

Answer 16

• Depression (low), anxiety, insomnia (low), OCD, mania (high) aggressive behavior, some eating disorders
• Pain modulation

Question 17

Histamine is found mainly in…

Answer 17

Neurons of posterior hypothalamus in tuberomammillary nucleus

• Histamine to forebrain implicated in alert state
• Excitatory to thalamus
• Excitatory/Inhibitory to cortical neurons

Question 18

I’m getting lazy. Tell me some things about adenosine.

Answer 18

• Important in alertness
• Receptors in thalamus and cortex (inhibitory effect)

**Caffeine may block adenosine receptors!

Question 19

Still a little lazy. GABA.

Answer 19

• Inhibitory
• Bezodiazephine, barbiturates are GABA agonists used to treatment for epilepsy, anxiety, and sedatives/anesthesia
• Valium is an effective muscle relaxant
• Alcohol affect INOTROPIC GABA receptors

Question 20

Excessive norepinephrine:

Reduced epinephrine:

Answer 20

• Mania

- Depression

Question 21

Significant catecholamine loss in…

Answer 21

Alzheimer’s and Parkinson’s

Question 22

Tricyclic antidepressives are involved in ________

Answer 22

increasing 5-HT to block reuptake (SSRI)

• Pineal gland has highest concentration of 5-HT (converted to melatonin)

Question 23

Describe endorphins

Answer 23

• Derived from POMC precursors to ACTH, major role in endocrine function
• EXCLUSIVELY in hypothalamus
• Act as depressants (i.e. Morphine)

Question 24

Where do endorphins project?

Answer 24

Hypothalamus, amygdala, Nucleus accumbens, septal area, thalamus, locus ceruleus

Question 25

______ are the most abundant opioid peptide and are highly present in the _______

Answer 25

Enkephalins; globus pallidus

• Pain modulation in dorsal horn

Question 26

Effect of glutamate?

Answer 26

• Long-term potentiation via NMDA-type receptors
• KINDLING-INDUCED SEIZURES
• Pain transmission (via Adelta and C fibers) and excitotoxicity in acute brain injury (inducing calcium influx chromatolysis)

Question 27

Where does glutamate project?

Answer 27

• Corticostriate and subthalamic projections to globus pallidus

**Glutamate from glutamine via glutaminase

Question 28

Some neurotoxins:

Answer 28

• Alpha-Bungarotoxin – irreversibly bind to nAchR
• Conotoxin – competitively bind to nAchR
• Betel nuts – Ach agonist
• Muscarine – Muscarinic agonist
• Muscimol – GABAa agonist

Question 29

What is Lambert-Eaton Myasthenic Syndrome?

Answer 29

Caused by presynaptic defect in Ach release, resulting in limb weakness, has an association with neoplasms –> autonomic dysfunction