Neuronal activity regulates long-term synaptic potentiation (LTP) by regulating
ID: 3482197 • Letter: N
Question
Neuronal activity regulates long-term synaptic potentiation (LTP) by regulating gene expression. You want to test a hypothesis that the effects of antidepressants are linked to changes in synaptic strength leading to shifts in excitability of neural circuits. You are assigned to examine how addition of Sertraline (SSRI) to cultured cortical neurons would affect the number and strength of excitatory and inhibitory synapses in a mixed culture of cortical and striatal neurons.
Answer all three questions below, specifying (a), (b), and (c) in your answer.
a) Based on what is known about the effects of Ketamine and barbiturates in depression and anxiety, what changes do you expect to see in the number and activity of excitatory and inhibitory synapses following chronic treatment with Sertraline.
b) CREB is an important transcription factor mediating activity-dependent gene expression. Activated CREB is phosphorylated, thus CREB activation can be assessed by measuring the proportion of phosphorylated CREB in your neuronal culture following chronic treatment with Sertraline. What changes in CREB phosphorylation do you expect to see?
c) You can do an unbiased screen for changes in protein expression following treatment with Sertraline. What proteins do you think you may find expressed at higher levels? Lower Levels? Explain why (based on your answer in (a)).
Explanation / Answer
a. Following long term treatment of Sertraline excitatory synapses increases in number and activity compared to inhibitory synapse so that it increases the level of serotonin level and helps in treating the depression.
b.In response to Sertraline treatment the CREB Phosphorylation increases as a result of up regulation. this indicated that the person is responding to the treatment.
c. Following sertraline treatment, protein expression of brain derived neurotrophic factor , neuroprotective protein increases whereas it decreases tumour necrosis factor.