Neurophysiology of rule switching in the corticostriatal circuit.

The ability to adjust behavioral responses to cues in a changing environment is crucial for survival. Activity in the medial Prefrontal Cortex (mPFC) is thought to both represent rules to guide behavior as well as detect and resolve conflicts between rules in changing contingencies. While lesion and pharmacological studies have supported a crucial role for mPFC in this type of set-shifting, an understanding of how mPFC represents current rules or detects and resolves conflict between different rules is still unclear. Meanwhile, medial dorsal striatum (mDS) receives major projections from mPFC and neural activity of mDS is closely linked to action selection, making the mDS a potential major player for enacting rule-guided action policies. However, exactly what is signaled by mPFC and how this impacts neural signals in mDS is not well known. In this review, we will summarize what is known about neural signals of rules and set shifting in both prefrontal cortex and dorsal striatum, as well as provide questions and directions for future experiments.

Development and function of the midbrain dopamine system: what we know and what we need to.

The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study.

Nucleus accumbens core lesions enhance two-way active avoidance.

The majority of work examining the nucleus accumbens core (NAc) has focused on functions pertaining to behaviors guided by appetitive outcomes. These studies have pointed to the NAc as being critical for motivating behavior toward desirable outcomes. For example, we have recently shown that lesions of the NAc impaired performance on a reward-guided decision-making task that required rats to choose between differently valued rewards. Unfortunately, much less is known about the role that the NAc plays in motivating behavior when aversive outcomes are predicted. To address this issue we asked if NAc lesions impact performance on a two-way active avoidance task in which rats must learn to shuttle back and forth in a behavioral training box in order to avoid a footshock predicted by an auditory tone. Although bilateral NAc lesions initially impaired reward-guided decision-making, we found that the same lesions improved acquisition and retention of two-way active avoidance.

Retrograde transynaptic pseudorabies virus infection of central autonomic circuits in neonatal rats.

Pseudorabies virus (PRV) is widely used to map synaptically-linked neural circuits in adult animals. The present study sought to determine whether PRV has similar utility in neonatal rats, and whether central PRV infection in neonates elicits astrocytic and microglia/macrophage responses similar to those that contribute to specific transynaptic neuronal infection in adult rats. Retrograde transneuronal infection of autonomic circuits was examined 24-64 h after injection of an attenuated strain of PRV (PRV-Bartha) into the ventral stomach wall of 1-day-old rats. Brain and spinal cord sections were processed for immunocytochemical detection of PRV. Alternate sections were processed for immunolocalization of glial fibrillary acidic protein (GFAP) to identify fibrous astrocytes, or for an antigen associated with the complement C3bi receptor (OX42) to identify microglia. As in adult rats, the number and distribution of infected CNS neurons in neonatal rats increased progressively with advancing post-inoculation survival. Infected CNS neurons initially were restricted to the thoracic intermediolateral cell column and the dorsal motor nucleus of the vagus. Longer survival times led to retrograde transynaptic infection of additional neurons in the thoracic spinal cord, nucleus of the solitary tract, ventrolateral medulla, and caudal raphe nuclei. At the longest post-inoculation intervals, infected neurons also were observed in the area postrema and in certain autonomic-related regions of the rostral brainstem, hypothalamus, and amygdala. Quantitative analysis of immunolabeling in the dorsal vagal complex demonstrated that regions containing neurons at early stages of viral infection displayed increased astrocytic GFAP immunostaining; conversely, areas containing neurons at later stages of infection were characterized by a significant loss of GFAP staining and a parallel increase of OX42 microglia/macrophage immunolabeling. We conclude that PRV is effectively transported through synaptically-linked CNS circuits in neonatal rats, and that spatiotemporally-ordered responses by non-neuronal cells may contribute to the synaptic specificity of transneuronal viral transport.