Biology subjects

Pino, G.

Publications and source records attributed to Pino, G..

4 recordsLinked to original sources

bioRxiv2024

Thermally-induced neuronal plasticity that mediates heat tolerance

Heat acclimation is an adaptive process that improves physiological performance and supports survival in the face of increasing environmental temperatures. Understanding the underlying mechanisms holds potential to mitigate health risks and reduces the steadily increasing number of heat-related casualties associated with global warming. Here we report the identification of a discrete group of hypothalamic preoptic neurons that transform to rheostatically increase their activity over the course of heat acclimation, a property required for mice to become heat tolerant. Peripheral thermo-afferent pathways via the parabrachial nucleus activate preoptic neurons and mediate acute heat-defense mechanisms in non-acclimated animals. However, long-term heat exposure promotes the preoptic neurons to gain intrinsically warm-sensitive activity, independent of thermo-afferent parabrachial input. Our data shows that their newly gained cell-autonomous warm-sensitivity is required to recruit peripheral heat tolerance mechanisms in acclimated animals. Mechanistically, we find a combination of increased sodium leak current and enhanced utilization of the Nav1.3 ion channel to drive their pacemaker-like, warm-sensitive activity. We propose a salient neuronal plasticity mechanism, adaptively driving acclimation to promote heat tolerance. HighlightsO_LIHeat acclimation induces tonic, warm-sensitive firing in hypothalamic VMPO neurons C_LIO_LITonic activity in VMPO neurons primes peripheral organs to gain heat tolerance capacity C_LIO_LIWarm-sensitive tonic firing recruits heat tolerance mechanisms in acclimated animals C_LIO_LINaV1.3 persistent sodium currents drive tonic, warm-sensitive firing in VMPO neurons C_LI

neuroscience↗

bioRxiv2022

Fear-Mouse Tracker (FMT): An open-source toolkit to track innate defensive behaviors with high precision

In the past years, machine-learning-based approaches to track animal poses with high spatial and temporal resolution have become available, but toolkits to extract, integrate, and analyze coordinate datasets in a user-friendly manner have lagged behind. Here, we introduce Fear-Mouse Tracker (FMT), a simple and open-source MATLAB-based pipeline to extract and quantitatively analyze DeepLabCut-derived coordinates of mice presented with threatening stimuli that commonly trigger innate defensive responses. This framework allows for unbiased quantitative estimations of stretch-attend posture (SAP) observed during risk assessment behaviors, as well as for measurements of the timing and extent of freezing and escape responses that follow the presentation of threatening stimuli such as a predator odor, or sweeping and looming stimuli resembling predator approaches. FMT is specially designed for users not very experienced in using programming languages, thus making it more accessible to a broader audience.

neuroscience↗

bioRxiv2021

Heterogeneous CaMKII-dependent synaptic compensations in CA1 pyramidal neurons from acute slices with dissected CA3

Prolonged changes in neural activity trigger homeostatic synaptic plasticity (HSP) allowing neuronal networks to operate in functional ranges. Cell-wide or input-specific adaptations can be induced by pharmacological or genetic manipulations of activity, and by sensory deprivation. Reactive functional changes caused by deafferentation may partially share mechanisms with HSP. Acute hippocampal slices constitute a suitable model to investigate relatively rapid (hours) pathway-specific modifications occurring after denervation and explore the underlying mechanisms. As Schaffer collaterals constitute a major glutamatergic input to CA1 pyramidal neurons, we conducted whole-cell recordings of miniature excitatory postsynaptic currents (mEPSCs) to evaluate changes over 12 hours after slice preparation and CA3 dissection. We observed an increment in mEPSCs amplitude and a decrease in decay time, suggesting synaptic AMPA receptor upregulation and subunit content modifications. Sorting mEPSC by rise time, a correlate of synapse location along dendrites, revealed amplitude raises at two separate domains. A specific frequency increase was observed in the same domains and was accompanied by a global, unspecific raise. Amplitude and frequency increments were lower at sites initially more active, consistent with local compensatory processes. Transient preincubation with a specific Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor either blocked or occluded amplitude and frequency upregulation in different synapse populations. Results are consistent with the concurrent development of different known CaMKII-dependent HSP processes. Our observations support that deafferentation causes rapid and diverse compensations resembling classical slow forms of adaptation to inactivity. These results may contribute to understand fast-developing homeostatic or pathological events after brain injury.

neuroscience↗

bioRxiv2020

Bi-allelic variants in TSPOAP1, encoding the active zone protein RIMBP1, cause autosomal recessive dystonia

Dystonia is a debilitating hyperkinetic movement disorder, frequently transmitted as a monogenic trait. Here, we describe homozygous frameshift, nonsense and missense variants in TSPOAP1, encoding the active zone RIM-binding protein 1 (RIMBP1), as a novel genetic cause of autosomal recessive dystonia in seven subjects from three unrelated families. Subjects carrying loss-of-function variants presented with juvenile- onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy. Conversely, subjects carrying a pathogenic missense variant (p.Gly1808Ser) presented with isolated adult-onset focal dystonia. In mice, complete loss of RIMBP1, known to reduce neurotransmission, led to motor abnormalities reminiscent of dystonia, decreased Purkinje cell dendritic arborization, and reduced numbers of cerebellar synapses. In vitro analysis of the p.Gly1808Ser variant showed larger spike-evoked calcium transients and enhanced neurotransmission, suggesting that RIMBP1-linked dystonia can be caused by either reduced or enhanced rates of spike-evoked release in relevant neural networks. Our findings establish a direct link between presynaptic RIMBP1 dysfunction and dystonia and highlight the critical role played by well-balanced neurotransmission in motor control and disease pathogenesis.

genetics↗