Rhythmic firing patterns in SCN: The role of circuit interactions

The suprachiasmatic nucleus (SCN) is believed to contain the main generator of circadian rhythmicity in mammals. In order to obtain further functional details of this, electrophysiological extracellular measurements in vitro were made. By means of an interspike interval distribution analysis, it is shown that there is a novel kind of neuronal firing pattern: the harmonic pattern. From these observations, we have developed a theoretical model based on possible filtering processes occurring during synaptic transmission. The model suffices to infer that regular ultradian oscillators could be an emergent property of circuit interactions of cells in the suprachiasmatic nucleus

Reductions in hypothalamic Gfap expression, glial cells and α-tanycytes in lean and hypermetabolic Gnasxl-deficient mice

BACKGROUND: Neuronal and glial differentiation in the murine hypothalamus is not complete at birth, but continues over the first two weeks postnatally. Nutritional status and Leptin deficiency can influence the maturation of neuronal projections and glial patterns, and hypothalamic gliosis occurs in mouse models of obesity. Gnasxl constitutes an alternative transcript of the genomically imprinted Gnas locus and encodes a variant of the signalling protein Gαs, termed XLαs, which is expressed in defined areas of the hypothalamus. Gnasxl-deficient mice show postnatal growth retardation and undernutrition, while surviving adults remain lean and hypermetabolic with increased sympathetic nervous system (SNS) activity. Effects of this knock-out on the hypothalamic neural network have not yet been investigated. RESULTS: RNAseq analysis for gene expression changes in hypothalami of Gnasxl-deficient mice indicated Glial fibrillary acid protein (Gfap) expression to be significantly down-regulated in adult samples. Histological analysis confirmed a reduction in Gfap-positive glial cell numbers specifically in the hypothalamus. This reduction was observed in adult tissue samples, whereas no difference was found in hypothalami of postnatal stages, indicating an adaptation in adult Gnasxl-deficient mice to their earlier growth phenotype and hypermetabolism. Especially noticeable was a loss of many Gfap-positive α-tanycytes and their processes, which form part of the ependymal layer that lines the medial and dorsal regions of the 3(rd) ventricle, while β-tanycytes along the median eminence (ME) and infundibular recesses appeared unaffected. This was accompanied by local reductions in Vimentin and Nestin expression. Hypothalamic RNA levels of glial solute transporters were unchanged, indicating a potential compensatory up-regulation in the remaining astrocytes and tanycytes. CONCLUSION: Gnasxl deficiency does not directly affect glial development in the hypothalamus, since it is expressed in neurons, and Gfap-positive astrocytes and tanycytes appear normal during early postnatal stages. The loss of Gfap-expressing cells in adult hypothalami appears to be a consequence of the postnatal undernutrition, hypoglycaemia and continued hypermetabolism and leanness of Gnasxl-deficient mice, which contrasts with gliosis observed in obese mouse models. Since α-tanycytes also function as adult neural progenitor cells, these findings might indicate further developmental abnormalities in hypothalamic formations of Gnasxl-deficient mice, potentially including neuronal composition and projections

Tracto retinohipotalamico en el conejo

Circadian rhythms are fluctuations with a period around 24 hrs and the most remarkable in humans is the awake-sleep cycle. In mammals these rhythms are under control of a master clock in the suprachiasmatic nucleus (SCN), in the brain. However these rhythms are endogenous, need to be synchronized to the external light-dark cycles in order to have an adaptive value for the individuals. Photic external information is transmitted through retinohypothalamic tract, a bundle of fibers from retina to SCN. In the present contribution we analyzed the anatomy and ontogenetic development of this tract in rabbits in two conditions, when their main synchronizer is food (postnatal days 1 and 9) and in adults when their main synchronizer is light, with aid of the tracer cholera toxin ß. Retinohypothalamic tract is present at postnatal days 1 and 9 when eyelids are closed and presents a gradual development; scarce fibers on postnatal day 1, but on day 9 it has a dense innervation, similar to adult subjects. It remains to determine whether the tract is functional at postnatal day 1 and 9, i.e., if responds to photic stimulation when the main synchronizer at these age is food, not light.Los ritmos circádicos son variaciones que ocurren en un período de aproximadamente 24 horas y el más notable en nuestra especie es el ciclo sueño-vigilia. En los mamíferos dichos ritmos están controlados por un reloj maestro que se localiza en el núcleo supraquiasmático (NSQ), ubicado en el cerebro. Estos ritmos son endógenos pero necesitan sincronizarse a los ciclos externos de luz-oscuridad para que tengan una función adaptativa a los organismos. La información fótica externa es transmitida a través del tracto retinohipotalámico, una haz de fibras que va de la retina hasta el núcleo NSQ. En el presente trabajo se estudió la anatomía y el desarrollo ontogenético de dicho tracto en el conejo en dos condiciones, cuando su sincronizador principal es el alimento (día postnatal 1 y 9) y en adultos cuando su principal sincronizador es la luz, con el trazador ß toxina de cólera. El tracto está presente desde los días 1 y 9 postnatal cuando los individuos aún no abren los ojos y presenta un desarrollo gradual de inervación en el NSQ. Esto es en el día 1 se observan escasas fibras en el núcleo, pero en el día 9 ya se observa una intensa inervación, la cual es similar a la del adulto. Sin embargo se debe determinar si tanto en el día 1 y 9 dicha inervación ya es funcional, esto es, si responde a la estimulación fótica ya que el principal sincronizador de estos sujetos es el alimento y no la luz

Rhythmic firing patterns in SCN: The role of circuit interactions

The suprachiasmatic nucleus (SCN) is believed to contain the main generator of circadian rhythmicity in mammals. In order to obtain further functional details of this, electrophysiological extracellular measurements in vitro were made. By means of an interspike interval distribution analysis, it is shown that there is a novel kind of neuronal firing pattern: the harmonic pattern. From these observations, we have developed a theoretical model based on possible filtering processes occurring during synaptic transmission. The model suffices to infer that regular ultradian oscillators could be an emergent property of circuit interactions of cells in the suprachiasmatic nucleus

Ryanodine-sensitive intracellular Ca2+ channels are involved in the output from the SCN circadian clock

Circadian clocks in health and diseas