The maturation of the prefrontal cortex (PFC) during adolescence is thought to be important for cognitive and affective development and mental health risk. Whereas many summaries of adolescent development have focused on dendritic spine pruning and gray matter thinning in the PFC during adolescence, we highlight recent rodent data from our laboratory and others to call attention to continued synapse formation and plasticity in the adolescent period in specific cell types and circuits. In particular, we highlight changes in inhibitory neurotransmission onto intratelencephalic (IT-type) projecting cortical neurons and late expansion of connectivity between the amygdala and PFC and the ventral tegmental area and PFC. Continued work on these "late blooming" synapses in specific cell types and circuits, and their interrelationships, [...]
Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies
A common human polymorphism in the gene that encodes brain derived neurotrophic factor (BDNF), Val66Met, is considered a marker of vulnerability for mental health issues and has been associated with cognitive impairment. An alternate framework has been proposed in which “risk alleles” are reinterpreted as “plasticity alleles” that confer vulnerability in adverse environments and positive effects in neutral or positive environments (Belsky et al., 2009). These frameworks produce divergent predictions for tests of learning and cognitive flexibility. Here, we examined multiple aspects of learning and cognitive flexibility in a relatively new BDNF Val66Met mouse model (BDNF Val68Met, Warnault et al., 2016), including multiple choice discrimination and reversal, go/no-go learning and reversal, and appetitive extinction learning. We found that mice homozygous [...]
Imaging Striatal Dopamine Release Using a Non-Genetically Encoded Near-Infrared Fluorescent Catecholamine Nanosensor
Neuromodulation plays a critical role in brain function in both health and disease. New optical tools, and their validation in biological tissues, are needed that can image neuromodulation with high spatial and temporal resolution, which will add an important new dimension of information to neuroscience research. Here, we demonstrate the use of a catecholamine nanosensor with fluorescent emission in the 1000-1300 nm near-infrared window to measure dopamine transmission in ex vivo brain slices. These near-infrared catecholamine nanosensors (nIRCats) represent a broader class of nanosensors that can be synthesized from non-covalent conjugation of single wall carbon nanotubes (SWNT) with single strand oligonucleotides. We show that nIRCats can be used to detect catecholamine efflux in brain tissue driven by both electrical stimulation [...]
Professor Wilbrecht's essay, Your Twelve-Year-Old Isn't Just Sprouting New Hair but Is Also Forming (and Being Formed by) New Neural Connections, appears in Think Tank: Forty Neuroscientists Explore the Biological Roots of Human Experience (David J. Linden, ed. 2018).