Parallel Interdigitated Distributed Networks within the Individual Estimated by Intrinsic Functional Connectivity

July 19, 2017

Braga RM, Buckner RL

Certain organizational features of brain networks present in the individual are lost when central tendencies are examined in the group. Here we investigated the detailed network organization of four individuals each scanned 24 times using MRI. We discovered that the distributed network known as the default network is comprised of two separate networks possessing adjacent regions in eight or more cortical zones. A distinction between the networks is that one is coupled to the hippocampal formation while the other is not. Further exploration revealed that these two networks were juxtaposed with additional networks that themselves fractionate group-defined networks. The collective networks display a repeating spatial progression in multiple cortical zones, suggesting that they are embedded within a broad macroscale gradient. Regions contributing to the newly defined networks are spatially variable across individuals and adjacent to distinct networks, raising issues for network estimation in group-averaged data and applied endeavors, including targeted neuromodulation.


A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish

July 12, 2017

Oteiza P, Odstrcil I, Lauder G, Portugues R, Engert F

When flying or swimming, animals must adjust their own movement to compensate for displacements induced by the flow of the surrounding air or water. These flow-induced displacements can most easily be detected as visual whole-field motion with respect to the animal's frame of reference. Despite this, many aquatic animals consistently orient and swim against oncoming flows (a behaviour known as rheotaxis) even in the absence of visual cues. How animals achieve this task, and its underlying sensory basis, is still unknown. Here we show that, in the absence of visual information, larval zebrafish (Danio rerio) perform rheotaxis by using flow velocity gradients as navigational cues. We present behavioural data that support a novel algorithm based on such local velocity gradients that fish use to avoid getting dragged by flowing water. Specifically, we show that fish use their mechanosensory lateral line to first sense the curl (or vorticity) of the local velocity vector field to detect the presence of flow and, second, to measure its temporal change after swim bouts to deduce flow direction. These results reveal an elegant navigational strategy based on the sensing of flow velocity gradients and provide a comprehensive behavioural algorithm, also applicable for robotic design, that generalizes to a wide range of animal behaviours in moving fluids.


Disrupted Prefrontal Regulation of Striatal Subjective Value Signals in Psychopathy

July 5, 2017

Psychopathy is a personality disorder with strong links to criminal behavior. While research on psychopathy has focused largely on socio-affective dysfunction, recent data suggest that aberrant decision making may also play an important role. Yet, the circuit-level mechanisms underlying maladaptive decision making in psychopathy remain unclear. Here, we used a multi-modality functional imaging approach to identify these mechanisms in a population of adult male incarcerated offenders. Psychopathy was associated with stronger subjective value-related activity within the nucleus accumbens (NAcc) during inter-temporal choice and with weaker intrinsic functional connectivity between NAcc and ventromedial prefrontal cortex (vmPFC). NAcc-vmPFC connectivity strength was negatively correlated with NAcc subjective value-related activity; however, this putative regulatory pattern was abolished as psychopathy severity increased. Finally, weaker cortico-striatal regulation predicted more frequent criminal convictions. These data suggest that cortico-striatal circuit dysregulation drives maladaptive decision making in psychopathy, supporting the notion that reward system dysfunction comprises an important neurobiological risk factor.


Ctip1 Controls Acquisition of Sensory Area Identity and Establishment of Sensory Input Fields in the Developing Neocortex

June 29, 2017

Abstract: While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive "sensory field" in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development.


Cited2 Regulates Neocortical Layer II/III Generation and Somatosensory Callosal Projection Neuron Development and Connectivity

June 15, 2017

Fame RM, MacDonald JL, Dunwoodie SL, Takahashi E, Macklis JD

The neocortex contains hundreds to thousands of distinct subtypes of precisely connected neurons, allowing it to perform remarkably complex tasks of high-level cognition. Callosal projection neurons (CPN) connect the cerebral hemispheres via the corpus callosum, integrating cortical information and playing key roles in associative cognition. CPN are a strikingly diverse set of neuronal subpopulations, and development of this diversity requires precise control by a complex, interactive set of molecular effectors. We have found that the transcriptional coregulator Cited2 regulates and refines two stages of CPN development. Cited2 is expressed broadly by progenitors in the embryonic day 15.5 subventricular zone, during the peak of superficial layer CPN birth, with a progressive postmitotic refinement in expression, becoming restricted to CPN of the somatosensory cortex postnatally. We generated progenitor-stage and postmitotic forebrain-specific Cited2 conditional knock-out mice, using the Emx1-Cre and NEX-Cre mouse lines, respectively. We demonstrate that Cited2 functions in progenitors, but is not necessary postmitotically, to regulate both (1) broad generation of layer II/III CPN and (2) acquisition of precise area-specific molecular identity and axonal/dendritic connectivity of somatosensory CPN. This novel CPN subtype-specific and area-specific control from progenitor action of Cited2 adds yet another layer of complexity to the multistage developmental regulation of neocortical development.

This study identifies Cited2 as a novel subtype-specific and area-specific control over development of distinct subpopulations within the broad population of callosal projection neurons (CPN), whose axons connect the two cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We found that Cited2 functions within subventricular zone progenitors to both broadly regulate generation of superficial layer CPN throughout the neocortex, and to refine precise area-specific development and connectivity of somatosensory CPN. Gaining insight into molecular development and heterogeneity of CPN will advance understanding of both diverse functions of CPN and of the remarkable range of neurodevelopmental deficits correlated with CPN/CC development