A mammalian enhancer trap resource for discovering and manipulating neuronal cell types

There is a continuing need for driver strains to enable cell-type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. However, since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (enhancertrap.bio.brandeis.edu)

Early motor influences on visuomotor transformations for reaching: a positive image of optic ataxia

Coding of reaching in the cerebral cortex is based on the operation of distributed populations of parietal and frontal neurons, whose main functional characteristics reside in their combinatorial power, i.e., in the capacity for combining different information related to the spatial aspects of reaching. The tangential distribution of reach-related neurons endowed with different functional properties changes gradually in the cortex and defines, in the parieto-frontal network, trends of functional proper ties. These visual-to-somatic gradients imply the existence of cortical regions of functional overlaps, i.e., of combinatorial domains, where the integration of different reach-related signals occurs. Studies of early coding of reaching in the mesial parietal areas show how somatomotor information, such as that related to arm posture and movement, influences neuronal activity in the very early stages of the visuomotor transformation underlying the composition of the motor command and is not added "downstream" in the frontal cortex. This influence is probably due to re-entrant signals traveling through fr onto-parietal-association connections. Together with the gradient architecture of the network and the reciprocity of cortico-cortical connections, this implies that coding of reaching cannot be regarded as a top-down, serial sequence of coordinate transformation, each performed by a given cortical area, but as a recursive process, where different signals are progressively matched and further elaborated locally, due to intrinsic cortical connections. This model of reaching is also supported by psychophysical studies stressing the parallel processing of the different relevant parameters and the "hybrid" nature of the reference frame where they are combined. The theoretical frame presented here can also offer a background fur a new interpretation of a well-known visuomotor disorder, due to superior parietal lesions, i.e., optic ataxia. More than a disconnection syndrome, this can now be interpreted as the consequence of the breakdown of the operations occurring in the combinatorial domains of the superior parietal segment of the parieto-frontal network

Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity

Retinoic acid-related orphan receptor beta (RORβ) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age in wildtype mice. Loss of RORβ delays excitatory input and disrupts gene expression and chromatin accessibility, with down-regulation of L4 and up-regulation of L5 genes, suggesting a disruption in cellular specification. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORβ, Thsd7a, is down-regulated without RORβ, and Thsd7a knock-out alone disrupts TCA organization in adult barrels

Social validation of component behaviors of following instructions, accepting criticism, and negotiating.

This study evaluated whether behaviors often taught as part of social skills training are judged favorably by others. Community judges evaluated the performances of people in various situations requiring one of three social skills: following instructions, accepting criticism, and negotiating to resolve conflicts. These skills were displayed in videotaped scenes by actors with and without mental retardation who acted out roles that had different types of authority relationships, and when different components or clusters of behavior (nonverbal, specific verbal, or general verbal behaviors) were performed well or poorly. The highest ratings by judges were of videotaped scenes that depicted correct use of all behaviors, regardless of which skill was being examined, whether or not the actor had mental retardation, or what the relationship was between the two actors. The lowest ratings were of videotaped scenes that depicted poor performance of all behaviors, and intermediate ratings were obtained when only some of the behaviors were performed poorly. These results, as well as the verbal responses of judges to questions, indicated that the different behaviors commonly used in teaching the skills of following instructions, accepting criticism, and negotiating are relevant to judgment of social performance, and are likely to be reinforced and maintained by social contingencies