Chemically Defined Circuits Flashcards
2 main sources of NEUROMODULATORY acetylcholine in CNS:
- pedunculopontine tegmental nuclei (lateral reticular formation)
- laterosdorsal tegmental nuclei (PAG, between midbrain and pons)
Project to thalamus, then cortex
Role of neuromodulatory acetylcholine?
Arousal, locomotor movements
Direct cholinergic input to cortex is from the ______
Nucleus basalis of Meynert
Direct cholinergic input to cortex is from the ______
- Medial septal nuclei
- Nucleus of the diagonal band
MAIN functions of acetylcholine in the CNS:
Attention, memory, learning
Blockage leads to delirium and memory deficits
Dopamine is found mainly in the ventral midbrain in…
- Substantia nigra pars compacta
- Ventral tegmental area
Cognitive, motor, neuroendocrine functions
3 projection systems of dopamine?
- 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)
Dysfunction of mesostriatal pathway leads to…
Parkinson’s (treat with dopaminergic agonists)
Overactivity of mesolimbic pathway leads to…
“Positive” symptoms of schizophrenia (hallucinations)
Often respond to dopaminergic agonists
Dysfunction of mesocortical pathway leads to…
Cognitive deficits and hypokinesia in Parkinson’s
“Negative” symptoms of schizophrenia
Norepinephrine comes from…
- Nucleus ceruleus
- Scattered nuclei in lateral tegmental area
Ascending projections reach entire forebrain
(also to cerebellum, brainstem, spinal cord)
Norepinephrine is both inhibitory and excitatory, but is mainly excitatory to the _______.
Functions include:
Thalamus
- Modulation of attention
- Sleep-wake states (locus ceruleus activity higher in wake)
- Mood
Norepinephrine-enhancing medications can treat…
- ADD
- Narcolepsy
Norepinephrine and serotonin together are important in…
Mood disorders (depression, manic-depressive) Anxiety disorders (OCD)
Serotonin is found in…
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
Rostral serotonin projections play a role in:
Caudal projections play a role in:
- Depression (low), anxiety, insomnia (low), OCD, mania (high) aggressive behavior, some eating disorders
- Pain modulation
Histamine is found mainly in…
Neurons of posterior hypothalamus in tuberomammillary nucleus
- Histamine to forebrain implicated in alert state
- Excitatory to thalamus
- Excitatory/Inhibitory to cortical neurons
I’m getting lazy. Tell me some things about adenosine.
- Important in alertness
- Receptors in thalamus and cortex (inhibitory effect)
**Caffeine may block adenosine receptors!
Still a little lazy. GABA.
- 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
Excessive norepinephrine:
Reduced epinephrine:
- Mania
- Depression
Significant catecholamine loss in…
Alzheimer’s and Parkinson’s
Tricyclic antidepressives are involved in ________
increasing 5-HT to block reuptake (SSRI)
- Pineal gland has highest concentration of 5-HT (converted to melatonin)
Describe endorphins
- Derived from POMC precursors to ACTH, major role in endocrine function
- EXCLUSIVELY in hypothalamus
- Act as depressants (i.e. Morphine)
Where do endorphins project?
Hypothalamus, amygdala, Nucleus accumbens, septal area, thalamus, locus ceruleus
______ are the most abundant opioid peptide and are highly present in the _______
Enkephalins; globus pallidus
- Pain modulation in dorsal horn
Effect of glutamate?
- 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)
Where does glutamate project?
- Corticostriate and subthalamic projections to globus pallidus
**Glutamate from glutamine via glutaminase
Some neurotoxins:
- Alpha-Bungarotoxin – irreversibly bind to nAchR
- Conotoxin – competitively bind to nAchR
- Betel nuts – Ach agonist
- Muscarine – Muscarinic agonist
- Muscimol – GABAa agonist
What is Lambert-Eaton Myasthenic Syndrome?
Caused by presynaptic defect in Ach release, resulting in limb weakness, has an association with neoplasms –> autonomic dysfunction
