Tissue non‐specific alkaline phosphatase (TNAP) is a key player of bone mineralization andTNAPgene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover,TNAPis also expressed by brain cells and the severe forms ofHPPare associated with neurological disorders, including epilepsy and brain morphological anomalies. However,TNAP's role in the nervous system remains poorly understood. To investigate its neuronal functions, we aimed to identify without anya priorithe metabolites regulated byTNAPin the nervous tissue. For this purpose we used¹H‐ and³¹P NMRto analyze the brain metabolome ofAlpl(Akp2) mice null forTNAPfunction, a well‐described model of infantileHPP. Among 39 metabolites identified in brain extracts of 1‐week‐old animals, eight displayed significantly different concentration inAkp2^−/−compared toAkp2^+/+andAkp2^+/−mice: cystathionine, adenosine,GABA, methionine, histidine, 3‐methylhistidine, N‐acetylaspartate (NAA), and N‐acetyl‐aspartyl‐glutamate, with cystathionine and adenosine levels displaying the strongest alteration. These metabolites identify several biochemical processes that directly or indirectly involveTNAPfunction, in particular through the regulation of ecto‐nucleotide levels and of pyridoxal phosphate‐dependent enzymes. Some of these metabolites are involved in neurotransmission (GABA, adenosine), in myelin synthesis (NAA,NAAG), and in the methionine cycle and transsulfuration pathway (cystathionine, methionine). Their disturbances may contribute to the neurodevelopmental and neurological phenotype ofHPP. image

Key questions in paleoneurology concern the timing and emergence of derived cerebral features within the human lineage. Endocasts are replicas of the internal table of the bony braincase that are widely used in paleoneurology as a proxy for reconstructing a timeline for hominin brain evolution in the fossil record. The accurate identification of cerebral sulci imprints in endocasts is critical for assessing the topographic extension and structural organisation of cortical regions in fossil hominins. High‐resolution imaging techniques combined with established methods based on population‐specific brain atlases offer new opportunities for tracking detailed endocranial characteristics. This study provides the first documentation of sulcal pattern imprints from the superolateral surface of the cerebrum using a population‐based atlas technique on extant human endocasts. Human crania from the Pretoria Bone Collection (South Africa) were scanned using micro‐CT. Endocasts were virtually extracted, and sulci were automatically detected and manually labelled. A density map method was applied to project all the labels onto an averaged endocast to visualise the mean distribution of each identified sulcal imprint. This method allowed for the visualisation of inter‐individual variation of sulcal imprints, for example, frontal lobe sulci, correlating with previous brain‐MRI studies and for the first time the extensive overlapping of imprints in historically debated areas of the endocast (e.g. occipital lobe). In providing an innovative, non‐invasive, observer‐independent method to investigate human endocranial structural organisation, our analytical protocol introduces a promising perspective for future research in paleoneurology and for discussing critical hypotheses on the evolution of cognitive abilities among hominins.

We examined the effect of adenosine and of adenosine A1 receptor blockage on short‐term synaptic plasticity in slices of adult mouse anterior piriform cortex maintained in vitro in an in vivo‐like ACSF. Extracellular recording of postsynaptic responses was performed in layer 1a while repeated electrical stimulation (5‐pulse‐trains, frequency between 3.125 and 100 Hz) was applied to the lateral olfactory tract. Our stimulation protocol was aimed at covering the frequency range of oscillatory activities observed in the olfactory bulb in vivo. In control condition, postsynaptic response amplitude showed a large enhancement for stimulation frequencies in the beta and gamma frequency range. A phenomenological model of short‐term synaptic plasticity fitted to the data suggests that this frequency‐dependent enhancement can be explained by the interplay between a short‐term facilitation mechanism and two short‐term depression mechanisms, with fast and slow recovery time constants. In the presence of adenosine, response amplitude evoked by low‐frequency stimulation decreased in a dose‐dependent manner (IC₅₀ = 70 μmol/L). Yet short‐term plasticity became more dominated by facilitation and less influenced by depression. Both changes compensated for the initial decrease in response amplitude in a way that depended on stimulation frequency: compensation was strongest at high frequency, up to restoring response amplitudes to values similar to those measured in control condition. The model suggested that the main effects of adenosine were to decrease neurotransmitter release probability and to attenuate short‐term depression mechanisms. Overall, these results suggest that adenosine does not merely inhibit neuronal activity but acts in a more subtle, frequency‐dependent manner.