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 for the Met allele show more efficient reversal learning in two different paradigms, but learn at rates comparable to Val homozygotes on the multiple choice discrimination task, a go/no-go task, and in appetitive extinction. Our results dissociate reversal performance from go/no-go learning and appetitive extinction and support the plasticity allele framework that suggests BDNF Met carriers are potentially more sensitive to changes in the environment.

Angela Vandenberg, Wan Chen Lin, Lung-Hao Tai, Dorit Ron, Linda Wilbrecht, Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies, 34 Developmental Cognitive Neuroscience 34–41 (2018)

Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies2019-02-02T21:38:12+00:00

Lung-Hao Tai’s collaborative work with Bo Li lab recently published

Lung-Hao Tai’s collaborative work with the Bo Li lab was recently published as: Marcus Stephenson-Jones, Kai Yu, Sandra Ahrens, Jason M. Tucciarone, Aile N. van Huijstee, Luis A. Mejia, Mario A. Penzo, Lung-Hao Tai, Linda Wilbrecht, Bo Li, A basal ganglia circuit for evaluating action outcomes, Nature, http://dx.doi.org/10.1038/nature19845 (2016).

Lung-Hao Tai’s collaborative work with Bo Li lab recently published2016-09-24T03:43:39+00:00

Rule learning enhances structural plasticity of long range axons in frontal cortex

Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore–exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and scales with the magnitude of experienced prediction errors. We conclude that rule learning sculpts frontal cortex interconnectivity and adjusts a thermostat for the explore–exploit balance.

Johnson C, Peckler H,Tai LH, Wilbrecht L., Rule learning enhances structural plasticity of long range axons in frontal cortex. Nature Communications (2016)

Rule learning enhances structural plasticity of long range axons in frontal cortex

Rule learning enhances structural plasticity of long range axons in frontal cortex2016-02-03T05:59:56+00:00

Review: Between the Primate and “Reptilian” Brain: Rodent Models Demonstrate the Role of the Corticostriatal Circuits in Decision Making

Decision making can be defined as the flexible integration and transformation of information from the external world into action. Recently, the development of novel genetic tools and new behavioral paradigms has made it attractive to study behavior of all kinds in rodents. By some perspectives, rodents are not an acceptable model for the study of decision making due to their simpler behavior often attributed to their less extensive cortical development when compared to non-human primates. We argue that decision making can be approached with a common framework across species. We review insights from comparative anatomy that suggest the expansion of cortical-striatal connectivity is a key development in evolutionary increases in behavioral flexibility. We briefly review studies that establish a role for corticostriatal circuits in integrative decision making. Finally, we provide an overview of a few recent, highly complementary rodent decision making studies using genetic tools, revealing with new cellular and tempo- ral resolution how, when and where information can be integrated and compared in striatal circuits to influence choice.

Lee AM et al. Between the primate and ‘reptilian’ brain: Rodent models demonstrate the role of corticostriatal circuits in decision making. Neuroscience (2015), http://dx.doi.org/10.1016/j.neuroscience.2014.12.042

 

Review: Between the Primate and “Reptilian” Brain: Rodent Models Demonstrate the Role of the Corticostriatal Circuits in Decision Making2015-01-31T21:27:19+00:00

Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value

In changing environments, animals must adaptively select actions to achieve their goals. In tasks involving goal-directed action selection, striatal neural activity has been shown to represent the value of competing actions. Striatal representations of action value could potentially bias responses toward actions of higher value. However, no study to date has demonstrated the direct effect of distinct striatal pathways in goal-directed action selection. We found that transient optogenetic stimulation of dorsal striatal dopamine D1 and D2 receptor–expressing neurons during decision-making in mice introduced opposing biases in the distribution of choices. The effect of stimulation on choice was dependent on recent reward history and mimicked an additive change in the action value. Although stimulation before and during movement initiation produced a robust bias in choice behavior, this bias was substantially diminished when stimulation was delayed after response initiation. Together, our data suggest that striatal activity is involved in goal-directed action selection.

Lung-Hao Tai*, A Moses Lee*, Nora Benavidez, Antonello Bonci, Linda Wilbrecht, Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value Nature Neuroscience 15, 1281–1289, (2012) doi:10.1038/nn.3188 (Full Text)

Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value2012-08-19T16:51:22+00:00