Homework 5

This problem set is due Wednesday (11/23/2022) at midnight. Please turn in your work by uploading to Canvas. If you have questions, please post them on the course forum, rather than emailing the course staff. This will allow other students with the same question to see the response and any ensuing discussion. The goal of this problem set is to learn how to decode spike trains by classification.

1. Clinical uses of brain stimulation

   a. Read this paper about the Orion system. What is one challenge that stands in the way of combining phosphenes for artificial vision?

   b. Read this article about Second Sight’s previous product. Brainstorm some ideas about how neurotechnology companies might structure their products to balance ongoing costs and patient welfare.

2. Getting genes to the right place using a viral vector

   Read this article for reference, and this article for reference.

   a. What are three examples of promoters can be used to target neurons?

   b. What does it mean for a transgene in a virus to be “FLEX”ed? (Note this reference from Lecture 19!)

   c. How would you limit expression of a transgene such that it would only be expressed during a short time window of a few weeks (for example to study memory of a particular event)? Hint: You could use a transgenic Cre-expressing animal, where Cre expression was controlled by another system.

3. Optogenetics

   a. What is a common name for the chemical that key to transducing light energy for optogenetics or vision?

   b. What is an inhibitory optogenetic protein could you virally express to silence excitatory neurons in a small region with light? If there is a local circuit with interneurons connecting to the excitatory neurons, what recipe of viral promoter and _excitatory_ optogenetic transgene would silence the excitatory neurons in the circuit?

   c. Imagine you wanted to express ChR2 selectively in the excitatory neurons that project from area dorsal CA1 of the hippocampus to the medial prefrontal cortex. How could you target these cells using a viral approach?

   d. If you wanted to activate neurons in the subthalamic nucleus at 130 Hz to mimic the excitatory aspect of deep brain stimulation, what would a good light-activated protein be?

   e. If you wanted to control the activity of a neuron bidirectionally (i.e., increase or decrease its firing), how could you do this using viral vector(s)?

4. DREADDS

   Read this review paper about DREADDs.

   a. Explain how you would use a DREADD system with a viral vector to inhibit neural activity in a small brain region during a 1 day learning experiment. Design your viral vector such that the inhibition will primarily be in excitatory neurons.

   b. If you were going to conduct the experiment from problem a. by activating the DREADD transgene using CNO delivered in the drinking water, what is one undesirable side effect that might happen?