Biology subjects

Esparza, J.

Publications and source records attributed to Esparza, J..

3 recordsLinked to original sources

bioRxiv2022

Quantifying the distribution of feature values over data represented in arbitrary dimensional spaces

BackgroundIdentifying the structured distribution (or lack thereof) of a given feature over a point cloud is a general research question. In the neuroscience field, this problem arises while investigating representations over neural manifolds (e.g., spatial coding), in the analysis of neurophysiological signals (e.g., auditory coding) or in anatomical image segmentation. New methodWe introduce the Structure Index (SI) as a graph-based topological metric to quantify the distribution of feature values projected over data in arbitrary D-dimensional spaces (neurons, time stamps, pixels). The SI is defined from the overlapping distribution of data points sharing similar feature values in a given neighborhood. ResultsUsing model data clouds we show how the SI provides quantification of the degree of local versus global organization of feature distribution. SI can be applied to both scalar and vectorial features permitting quantification of the relative contribution of related variables. When applied to experimental studies of head-direction cells, it is able to retrieve consistent feature structure from both the high- and low-dimensional representations. Finally, we provide two general-purpose examples (sound and image categorization), to illustrate the potential application to arbitrary dimensional spaces. Comparison with existing methodsMost methods for quantifying structure depend on cluster analysis, which are suboptimal for continuous features and non-discrete data clouds. SI unbiasedly quantifies structure from continuous data in any dimensional space. ConclusionsThe method provides versatile applications in the neuroscience and data science fields HighlightsO_LIThe Structure Index is a graph-based topological metric C_LIO_LIIt quantifies the distribution of feature values in arbitrary dimensional spaces C_LIO_LIIt can be applied to both scalar and vectorial features C_LIO_LIWhen applied to the head-direction neural system, it extracts concordant information from high- and low-dimensional representations C_LIO_LIIt can be extended to sound and image categorization, expanding the range of applications C_LI

neuroscience↗

bioRxiv2021

INTEROCEPTIVE INFORMATION OF PHYSICAL VIGOR: OREXIN NEURONS GAUGE CIRCULATING IGF-I FOR MOTIVATIONAL MOTOR OUTPUT

The brain relies on interoceptive feedback signals to regulate bodily functions. Mice with low serum IGF-1 levels (LID mice) exhibit reduced spontaneous running, a behavior that normalizes after sustained systemic IGF-1 treatment. This observation led us to hypothesize that circulating IGF-1--a key regulator of skeletal muscle and bone mass that crosses the blood-brain barrier during physical activity--may convey body vigor information to the brain. Since hypothalamic orexin neurons, that are involved in regulating physical activity, express IGF-1 receptors (IGF-1R) and are modulated by this growth factor, we hypothesized that these neurons might gauge circulating IGF-1 levels to modulate physical activity. Indeed, inactivation of IGF-1R in mouse orexin neurons (Firoc mice) was associated to less time spent in free running. These mice maintain physical fitness but display altered mood and are less sensitive to the rewarding actions of exercise. Further, in response to exercise, Firoc mice showed limited c-fos activation of hypothalamic orexin neurons and monoaminergic neurons of the ventro-tegmental area (VTA) in the brainstem. This area is involved in the rewarding component of exercise that seems to be modulated by IGF-1, as mice receiving systemic IGF-1 showed increased c-fos expression in VTA neurons, while mice with reduced IGF-1R expression in VTA neurons showed no improved mood after exercise. Collectively, these results suggest that circulating IGF-1 is gauged by orexin neurons to modulate physical activity, and that VTA neurons convey the rewarding properties of exercise through direct actions of IGF-1 on them. Hence, serum IGF-1 may constitute an interoceptive signal acting onto orexin/VTA neurons to modulate physical activity according to physical vigor (muscle and bone mass).

neuroscience↗

bioRxiv2021

INSULIN-LIKE GROWTH FACTOR I SENSITIZATION REJUVENATES SLEEP PATTERNS IN OLD MICE

Sleep disturbances are common during aging. Compared to young animals, old mice show altered sleep structure, with changes in both slow and fast electrocorticographic (ECoG) activity and fewer transitions between sleep and wake stages. Insulin-like growth factor I (IGF-I), which is involved in adaptive changes during aging, was previously shown to increase ECoG activity in young mice and monkeys. Furthermore, IGF-I shapes sleep architecture by modulating the activity of mouse orexin neurons in the lateral hypothalamus (LH). We now report that both ECoG stimulation and activation of orexin neurons by systemic IGF-I is abrogated in old mice. Moreover, stimulation of orthodromically activated LH neurons by either systemic or local IGF-I in young mice is absent in old mice. As orexin neurons of old mice show markedly increased IGF-I receptor (IGF-IR) levels, suggesting loss of sensitivity to IGF-I, we treated old mice with AIK3a305, a novel IGF-IR sensitizer, and observed restored responses to IGF-I and rejuvenation of sleep patterns. Thus, disturbed sleep structure in aging mice may be related to impaired IGF-I signaling onto orexin neurons, reflecting a broader loss of IGF-I activity in the aged mouse brain.

neuroscience↗