Neurobiology 7 Flashcards
What two categories can neuromodulators be divided into?
Wide projecting.
Local projecting.
Give two examples of wide projecting neuromodulators.
Acetylcholine.
Dopamine
Give two examples of local projecting neuromodulators.
Many peptides (somatostatin). Adenosine.
What do neuromodulators typically act through?
GPCRs - signalling via second messengers/protein kinases.
What is volume transmission?
When local neuromodulators are not released at a specific synapse, but instead diffuse to influence a group of neurons.
Where is dopamine synthesised?
Substantia nigra and the ventral tegmental area (VTA) - dopamine neurons found in clusters in these areas of brain stem.
Do dopamine neurons typically have long or short axons?
Long
Where is noradrenaline synthesised?
In the locus ceruleus.
Briefly describe dopamine synthesis.
L-DOPA is produced from L-tyrosine by tyrosine hydroxylase. This is converted to dopamine by DOPA decarboxylase.
What does DOPA decarboxylase require as a coenzyme?
pyridoxal phosphate.
What does monoamine oxidase do?
It is the transporter that puts dopamine into vesicles.
What genes must be switched on to make a dopamine neuron?
Tyrosine hydroxylase, DOPA decarboxylase and the monoamine oxidase genes
Briefly describe adrenaline synthesis.
Dopamine beta-hydroxylase catalyses the production of noradrenaline from dopamine.
Phenylethanolamine N-methyltransferase catalyses the conversion of noradrenaline to adrenaline.
Is dopamine used in volume (non-synaptic) transmission?
Yes.
What do dopamine neurons look like in the brain (striatum)?
The axon splits at the striatum to form a huge axonal cloud.
What regions of the brain do the dopamine neurons in the SN project to?
Project into the midbrain to the striatum and neocortex.
Give examples of dopamine neurons functions.
in CNS
Control blood flow to brain.
Motor control - initiates voluntary responses.
Behaviour control.
Give examples of dopamine neurons functions outside the CNS.
D1 dopamine receptor mediated renin secretion in the kidney.
Dopamine reduces gap junction communication between neurons in response to light intensity - helps retina switch from rod to cones.
Name the two main types of dopamine GPCRs
D1-like (including D1 and D5)
D2-like (including D2, 3 and 4).
What type of receptor is D1 and where is found?
Excitatory and is expressed in the adrenal cortex.
What does an excitatory signal to the D1 receptor do?
Stimulates the adrenal cortex to produce cAMP via the activation of a G protein. Results in activation of PKA and a phosphatase inhibitor - causing ion channels to be phosphorylated.
What type of receptor is D2?
An inhibitory receptor.
What does the combination of D1 and D2 allow for?
Fluid motor responses.
What does shortage of dopamine result in? (symptoms wise)
Indecisive personality and difficulty with body movement.
What is Parkinson’s disease treated with?
L-DOPA - can cross blood-brain barrier.
converted to dopamine in brain
What symptoms does excess dopamine cause?
More arousal to the motivational signal - leads to ADD and possible schizophrenia.
