Computational modeling can be used to reveal insights into the mechanisms and potential side effects of a new drug. Here we will focus on two major diseases: diabetes, which affects 1 in 10 people in North America, and hypertension, which affects 1 in 3 adults. For diabetes, we are interested in a class of relatively novel drug treatment, the SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors). E.g., Dapagliflozin, Canagliflozin, and Empagliflozin. We conduct simulations to better understand any side effect these drugs may have on our kidneys (which are the targets of SGLT2 inhibitors). Interestingly, these drugs may have both positive and negative side effects. For hypertension, we want to better understand the sex differences in the efficacy of some of the drug treatments. Women generally respond better to ARBs (angiotensin receptor blockers) than ACE inhibitors (angiontensin converting enzyme inhibitors), whereas the opposite is true for men. We have developed the first sex-specific computational model of blood pressure regulation, and applied that model to assess whether the ”one-size-fits-all” approach to blood pressure control is appropriate with regards to sex.[-]

In this talk, I will summarize some of our results on the properties of hippocampal place cells in rats that solve various spatial navigation tasks. Several of these properties are directly relevant to their role in navigation, including the phenomenon of local remapping, overdispersion (variability in firing), and goal-related firing, and thus emphasize the participation of place cells in the coding of spatial information and the computation of optimal paths.[-]

Start the video and click on the track button in the timeline to move to talk 1, 2 and to the discussion.

- Talk 1: Paul Apicella - Striatal dopamine and acetylcholine mechanisms involved in reward-related learning

The midbrain dopamine system has been identified as a major component of motivation and reward processing. One of its main targets is the striatum which plays an important role in motor control and learning functions. Other subcortical neurons work in parallel with dopamine neurons. In particular, striatal cholinergic interneurons participate in signaling the reward-related significance of stimuli and they may act in concert with dopamine to encode prediction error signals and control the learning of stimulus–response associations. Recent studies have revealed functional cooperativity between these two neuromodulatory systems of a complexity far greater than previously appreciated. In this talk I will review the difference and similarities between dopamine and acetylcholine reward-signaling systems, the possible nature of reward representation in each system, and discuss the involvement of striatal dopamine-acetylcholine interactions during leaning and behavior.

- Talk 2: Yonatan Loewenstein - Modeling operant learning: from synaptic plasticity to behavior

- Discussion with Paul Apicella and Yonatan Loewenstein[-]