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Summary: The extended amygdala has dominated research on the neural circuitry of fear and anxiety, but the septohippocampal axis also plays an important role. The lateral septum (LS) is thought to suppress fear and anxiety through its outputs to the hypothalamus. However, this structure has not yet been dissected using modern tools. The type 2 CRF receptor (Crfr2) marks a subset of LS neurons whose functional connectivity we have investigated using optogenetics. Crfr2 + cells include GABAergic projection neurons that connect with the anterior hypothalamus. Surprisingly, we find that these LS outputs enhance stress-induced behavioral measures of anxiety. Furthermore, transient activation of Crfr2 + neurons promotes, while inhibition suppresses, persistent anxious behaviors. LS Crfr2 + outputs also positively regulate circulating corticosteroid levels. These data identify a subset of LS projection neurons that promote, rather than suppress, stress-induced behavioral and endocrinological dimensions of persistent anxiety states and provide a cellular point of entry to LS circuitry. [Copyright &y& Elsevier]

Background: Radial glia comprise a molecularly defined neural progenitor population but their role in neurogenesis has remained contested due to the lack of a single universally accepted genetic tool for tracing their progeny and the inability to distinguish functionally distinct developmental stages. Results: By direct comparisons of Cre/loxP lineage tracing results obtained using three different radial glial promoters (Blbp, Glast, and hGFAP), we show that most neurons in the brain are derived from radial glia. Further, we show that hGFAP promoter induction occurs in ventral telencephalic radial glia only after they have largely completed neurogenesis. Conclusion: These data establish the major neurogenic role of radial glia in the developing central nervous system and genetically distinguish an early neurogenic Blbp+Glast+hGFAP- stage from a later gliogenic Blbp+Glast+hGFAP+ stage in the ventral telencephalon. [ABSTRACT FROM AUTHOR]

Radial glia function during CNS development both as neural progenitors and as a scaffolding supporting neuronal migration. To elucidate pathways involved in these functions, we mapped in vivo the promoter for Blbp, a radial glial gene. We show here that a binding site for the Notch effector CBF1 is essential for all Blbp transcription in radial glia, and that BLBP expression is significantly reduced in the forebrains of mice lacking the Notch1 and Notch3 receptors. These results identify Blbp as the first predominantly CNS-specific Notch target gene and suggest that it mediates some aspects of Notch signaling in radial glia. [ABSTRACT FROM AUTHOR]

Radial glial cells function during CNS development as neural progenitors, although their precise contribution to neurogenesis remains controversial. Recent work has argued that regional differences may exist regarding the neurogenic potential of radial glia. Here, we show that the vast majority of neurons in all brain regions derive from radial glia. Cre/loxP fate mapping and clonal analysis demonstrate that radial glia throughout the CNS serve as neuronal progenitors and that radial glia within different regions of the CNS pass through their neurogenic stage of development at distinct time points. Thus, radial glial populations within different CNS regions are not heterogeneous with regard to their potential to generate neurons versus glia. [Copyright &y& Elsevier]

Presents an introduction to the May 2005 issue of the journal "Cell."

Oxytocin (Oxt) neurons regulate diverse physiological responses via direct connections with different neural circuits. However, the lack of comprehensive input-output wiring diagrams of Oxt neurons and their quantitative relationship with Oxt receptor (Oxtr) expression presents challenges to understanding circuit-specific Oxt functions. Here, we establish a whole-brain distribution and anatomic connectivity map of Oxt neurons, and their relationship with Oxtr expression using high-resolution 3D mapping methods in adult male and female mice. We use a flatmap to describe Oxt neuronal expression in four hypothalamic domains including under-characterized Oxt neurons in the tuberal nucleus (TU). Oxt neurons in the paraventricular hypothalamus (PVH) broadly project to nine functional circuits that control cognition, brain state, and somatic visceral response. In contrast, Oxt neurons in the supraoptic (SO) and accessory (AN) nuclei have limited central projection to a small subset of the nine circuits. Surprisingly, quantitative comparison between Oxt output and Oxtr expression showed no significant correlation across the whole brain, suggesting abundant indirect Oxt signaling in Oxtr-expressing areas. Unlike output, Oxt neurons in both the PVH and SO receive similar monosynaptic inputs from a subset of the nine circuits mainly in the thalamic, hypothalamic, and cerebral nuclei areas. Our results suggest that PVH-Oxt neurons serve as a central modulator to integrate external and internal information via largely reciprocal connection with the nine circuits while the SO-Oxt neurons act mainly as unidirectional Oxt hormonal output. In summary, our Oxt wiring diagram provides anatomic insights about distinct behavioral functions of Oxt signaling in the brain. [ABSTRACT FROM AUTHOR]

Feeding can be inhibited by multiple cues, including those associated with satiety, sickness or unpalatable food. How such anorexigenic signals inhibit feeding at the neural circuit level is not completely understood. Although some inhibitory circuits have been identified, it is not yet clear whether distinct anorexigenic influences are processed in a convergent or parallel manner. The amygdala central nucleus (CEA) has been implicated in feeding control, but its role is controversial. The lateral subdivision of CEA (CEl) contains a subpopulation of GABAergic neurons that are marked by protein kinase C-δ (PKC-δ). We found that CEl PKC-δ+ neurons in mice were activated by diverse anorexigenic signals in vivo, were required for the inhibition of feeding by such signals and strongly suppressed food intake when activated. They received presynaptic inputs from anatomically distributed neurons activated by different anorexigenic agents. Our data suggest that CEl PKC-δ+ neurons constitute an important node that mediates the influence of multiple anorexigenic signals. [ABSTRACT FROM AUTHOR]