Major neurochemical pathways

Question 1

Dopaminergic pathways

Answer 1

• 3 types
  1. long paths: nigrostriatal, mesocortical and mesolimbic
  2. short paths: tuberoinfundibular and incertohypothalamic pathway
  3. ultrashort paths: found in amacrine cells in the retina and in the olfactory system

Question 2

Nigrostriatal pathway

Answer 2

• extrapyramidal pathway that is crucial for motor control
• most of the brain’s dopamine
• originates in the substantia nigra and travels to the amygdala and striatum via the medial forebrain bundle
• dopamine deficiency in Parkinsons disease or dopamine blockade due to antipsychotics can cause extrapyramidal side effects

Question 3

Mesolimbic pathway

Answer 3

• originates from ventral tegmental area and goes to the nucleus accumbens and hippocampus via medial forebrain bundle
• blockade of dopamine produces desirable antipsychotic effect by controlling positive psychotic symptoms

Question 4

Mesocortical pathway

Answer 4

• Originates in the Ventral Tegmental area and travels to the cingulate cortex and prefrontal regions via medial forebrain bundle
• low levels of dopamine or dopamine blockade in this tract is associated with negative symptoms (alogia, anhedonia, amotivation and apathy)

Question 5

Tuberoinfundibular pathway

Answer 5

• originates in hypothalamus and travels to the pituitary via the portal vessels
• dopamine acts as prolactin inhibitory hormone
• dopamine blockade serves to increase prolactin level

Question 6

Incertohypothalamic pathway

Answer 6

• internal connections within hypothalamus

- dopamine blockade causes disturbed thermoregulation and possible weight gain

Question 7

Cholinergic pathways

Answer 7

2 major cholinergic pathways

1. brainstem pathway
2. basal forebrain pathway

Question 8

Brainstem pathway

Answer 8

• cholinergic pathway
• forms part of the ARAS -ascending reticular activating system
• important for maintaining wakefulness and REM sleep state
• originates from pedunculopontine and laterodorsal tegmental nuclei and innervates thalamic relay neurons and reticular nuclei

Question 9

Basal forebrain pathway

Answer 9

• cholinergic pathway
• originates at the nucleus basalis of meynert in the basal forebrain and projects to the hippocampus, frontal cortex and amygdala
• degeneration of this pathway is implicated in Alzheimers

Question 10

Serotonergic pathways

Answer 10

• originate in the midbrain dorsal and medial raphe nuclei

- ascend to innervate the entire cortex, basal ganglia, thalamus and also descend to the spinal cord

Question 11

Noradrenergic pathways

Answer 11

-originates at the locus coeruleus (pons) and ascends to most of the cortex via the medial forebrain bundle

Question 12

Glutamatergic system

Answer 12

• glutamate is the most common excitatory neurotransmitter in the brain
• as a result almost all cortical descending tracts (from pyramidal cells) rely on glutamate for neurotransmission
• this large output of corticofugal fibres makes up most of the corona radiata
• all association and commisural fibres also use glutamatergic transmission
• many thalamic neurons are glutamatergic
• thalamocortical projections are also glutamatergic
• cerebellar output from deep nuclei, subthalamic nuclei to globus pallidus projections and braintem to spinal cord projections are also predominantly glutamatergic

Question 13

GABAergic system

Answer 13

• primary inhibitory neurotransmitter in the brain
• no specific pathway
• GABA is the major transmitter for cerebral interneurons throughout the cortex

Question 14

Interneurons

Answer 14

• usually short neurons
• connect two other neurons
• dont carry motor or sensory information but serve to modulate local neural circuitry
• 2 subtypes: parvalbumin-expressing interneurons and somatostatin expressing interneurons

Question 15

Parvalbumin (PV)-expressing interneurons

Answer 15

• 40% of interneurons
• reduction of these is seen in the frontal cortex in schizophrenia
• 2 subtypes: Basket cells and chandelier cells

Question 16

Somatostatin (SST)-expressing interneurons

Answer 16

• 30% of interneurons

- also called Martinotti cells

Question 17

Basket cells

Answer 17

• receive direct input from thalamocortical projections
• form synapses with the soma or dendrites of the pyramidal neurons
• provide excitatory-inhibitory balance in the cortex

Question 18

Chandelier cells

Answer 18

• form csynapses with the proximal axonal hillock of pyramidal neurons
• they may have an overall excitatory role by serving short-circuit the action potential propagation
• role not actually clear