Thurs, Nov 19 (3.45 PM – 4.05 PM)

Neural Circuits Mediating the Behavioral Effects of Chronic Stress and Antidepressants in Male and Female Mice
Chronic stressful experiences can precipitate mood disorders in humans and maladaptive affective behaviors in rodents. However, most rodent chronic stress paradigms were designed in males and are less effective in females. First, I’ll briefly describe two new stress paradigms that are effective in both male and female mice. Then, using those stress paradigms, I’ll explain the importance of dentate gyrus granule cells in mediating the beneficial effects of antidepressants on avoidance behaviors. Finally, I’ll explain the maladaptive effects of chronic stress on motivation and reward behaviors, which have high translational value for mood disorders such as depression.

Thurs, Nov 19 (4.10 PM – 4.30 PM)

Cyfip1 Mediates Addiction Relevant Phenotypes in Mice
Cocaine is a common drug of abuse that produces persistent changes in synaptic function and plasticity in the NAc, which results in addiction, but the cause of the differential predisposition to addiction remains largely unknown. Cytoplasmic FMR1-interacting protein (CYFIP 1) has been identified as a risk factor for several neuropsychiatric disorders including schizophrenia, intellectual disability, and autism in humans. To test if the cocaine related behavioral responses are affected when Cyfip1 levels are reduced, we performed open field tests in mice carrying a Cyfip1 mutation (Cyfip1+/-) and compared locomotor activity in control conditions and in response to cocaine. Cocaine-induced increase in locomotor response is blunted in Cyfip1+/- mice and in male mice more than female. A cocaine-conditioned place preference paradigm showed increased cocaine seeking in Cyfip1+/- mice. To add a self-controlling element and better simulate the pathophysiology of drug addiction in humans, we have used a reward-based touchscreen task. Preliminary results confirm the effect of Cyfip1 deficiency in reward-related decision-making. Clarifying Cyfip1’s role in cocaine response and NAc plasticity, which is a previously unexamined target, may be relevant for a variety of disease-related genes with similar functions.

Thurs, Nov 19 (4.35 PM – 4.55 PM)

Neural Mechanisms that Support Learning in Circuits with Significant Cellular Deficits
The corticostriatal circuit has been identified as a vital pathway for associative learning. However, this circuit is permanently altered by a transient developmental sensory deprivation. How learning is maintained in such conditions is unclear. Here, we used whole cell recording from a functional corticostriatal slice preparation to measure changes to the cellular and synaptic properties of striatal medium spiny neurons as adult gerbils were learning a sound discrimination task. In both groups, learning was accompanied by the dichotomous trafficking of GABAA-α1 subunit containing receptors.  Subsequently inhibitory tone in both groups moved towards the same mean during acquisition before returning to baseline as the animals mastered the task. Furthermore, a significant deficit to firing rate in the sensory deprived group was briefly compensated for by changes to intrinsic cellular properties during the acquisition phase of the task.  The firing rate deficit in this group then re-emerged as the animals mastered the task.  Together, these results demonstrate a form of learning related plasticity that allows significant cellular and synaptic deficits to be compensated for briefly.  This novel form of plasticity has implications for a neural mechanism that support learning in many neurological disorders.