Question

Dopaminergic neurons are found in the nucleus accumbens (IB word). Why do we need a nucleus accumbens? [1]

What is the ‘secondary messenger’ concept? [1]

Slow receptors can modulate Fast receptors. How? [2]

Opioids bind to opioid receptors on widely distributed pain pathways. Since they themselves are GPCRs they can act at a distance far from the opioid receptor.   What effect do opioids have on the pre- and post-synaptic membranes of neurons in the pain pathways? [4]

Answer 1

1.The nucleus accumbens definitely plays a central role in the reward circuit. Its operation is based chiefly on two essential neurotransmitters: dopamine, which promotes desire, and serotonin, whose effects include satiety and inhibition.The most important function of nucleus accumbens is to process and analyze the rewarding and reinforcing stimuli. It also plays a role in aversive behavior and regulation of sleep. It is also important in spatial and instrumental learning. Addiction is the major clinical condition associated with the nucleus accumbens.

2.Secondary messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intracellular signals, a non-local form or cell signaling, encompassing both first messengers and second messengers, are classified as juxtacrine, paracrine, and endocrine depending on the range of the signal.) Second messengers trigger physiological changes at cellular level such as proliferation, differentiation, migration, survival, apoptosis and depolarization.Examples of second messenger molecules include cyclic AMP, cyclic GMP, inositol trisphosphate, diacylglycerol, and calcium.

3.Fast-acting neurotransmitters bind directly to ligand-gated ion channels to initiate a rapid response (<1 millisecond)

• Slow-acting neurotransmitters bind to G-protein coupled receptors to initiate a slower response (milliseconds – minute)Slow-acting neurotransmitters trigger second messenger pathways within the post-synaptic cell, which allows for:
• A longer, more sustained duration of action (i.e. ion channels remain open for longer to mediate greater depolarisation)
• Long term alterations to cellular activity to improve synaptic transfer (i.e. increased expression of ion channels)Slow-acting neurotransmitters are called neuromodulators because they can modulate the efficiency of synaptic transfer

• Examples of fast-acting neurotransmitters include glutamate (excitatory) and GABA (inhibitory)
• Examples of slow-acting neurotransmitters include dopamine, serotonin, acetylcholine and noradrenaline

By modulating the efficiency of synaptic transfer, slow-acting neurotransmitters can regulate fast synaptic transmission.