Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function Ca2+ stores. Here we examined the these stores in hippocampal pyramidal neurons. We found back-propagating action potentials (bpAPs) could elicit release from lysosomes dendrites. This triggered fusion with plasma membrane, resulting Cathepsin B. B increased activity matrix metalloproteinase 9 (MMP-9), an enzyme involved extracellular (ECM) remodelling and...

Abstract Achieving intravital optical imaging with diffraction-limited spatial resolution of deep-brain structures represents an important step toward the goal understanding mammalian central nervous system 1–4 . Advances in wavefront-shaping methods and computational power have recently allowed for a novel approach to high-resolution imaging, utilizing deterministic light propagation through optically complex media and, particular importance this work, multimode fibers (MMFs) 5–7 We report...

Information processing is energetically expensive. In the mammalian brain, it unclear how information coding and energy use are regulated during food scarcity. Using whole-cell recordings two-photon imaging in layer 2/3 mouse visual cortex, we found that restriction reduced AMPA receptor conductance, reducing synaptic ATP by 29%. Neuronal excitability was nonetheless preserved a compensatory increase input resistance depolarized resting potential. Consequently, neurons spiked at similar...

Active dendrites impact sensory processing and behaviour. However, it remains unclear how active dendritic integration relates to somatic output in vivo. We imaged semi-simultaneously GCaMP6s signals the soma, trunk distal tuft of layer 5 pyramidal neurons awake mouse primary visual cortex. found that apical were dominated by widespread, highly correlated calcium transients throughout tuft. While these coupled transients, frequency was decrease a distance-dependent manner from soma Ex vivo...

Acidic Ca 2+ store–mediated mGluR signaling underlies synaptic plasticity in hippocampal neurons.

Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus expression—pre- or postsynaptic—is highly variable. Here we introduce a theoretical framework which long-term plasticity performs an optimization postsynaptic response statistics toward given mean with minimal variance. Consequently, state synapse at time induction determines ratio pre- and modifications. Our theory explains experimentally observed expression loci...

Hebbian plasticity is thought to require glutamate signalling. We show this not the case for hippocampal presynaptic long-term potentiation (LTPpre), which expressed as an increase in transmitter release probability (Pr). find that LTPpre can be induced by pairing pre- and postsynaptic spiking absence of induction involves a non-canonical mechanism retrograde nitric oxide signalling, triggered Ca2+ influx from L-type voltage-gated channels, NMDA receptors (NMDARs), does release. When occurs,...

Voltage-dependent Ca2+ channels (VGCC) represent the principal source of ions driving evoked neurotransmitter release at presynaptic boutons. In mammals, influx is mediated mainly via P/Q-type and N-type VGCC, which differ in their properties. Changes relative contributions tune neurotransmission both during development Hebbian plasticity. However, whether this represents a functional motif also present other forms activity-dependent regulation unknown. Here, we study role VGCC homeostatic...

A growing body of evidence suggests that lysosomes, which have traditionally been regarded as degradative organelles, can function Ca2+ stores, regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). We previously demonstrated in hippocampal pyramidal neurons, activity-dependent release from these stores triggers fusion lysosome with plasma membrane. found physiological role this Ca2+-dependent was to maintain long-term structural enlargement dendritic spines...

Despite evidence that presynaptic efficacy and plasticity influence circuit function behavior

Abstract Active dendrites impact sensory processing and behaviour. However, it remains unclear how active dendritic integration relates to somatic output in vivo . We imaged semi-simultaneously GCaMP6s signals the soma, trunk distal tuft of layer 5 pyramidal neurons awake mouse primary visual cortex. found that apical were dominated by widespread, highly correlated calcium transients throughout tuft. While these coupled transients, frequency was decrease a distance-dependent manner from soma...

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...

<title>Abstract</title> Mixed outcomes in clinical trials of amyloid β-lowering agents for Alzheimer’s disease (AD) make the identification alternative candidate molecular targets therapy a priority. However, limited understanding pathways mediating effects β on synaptic and cognitive function hampers these efforts. Here, we uncover an ENaC-Ca_V2.3-PKC-GSK-3β signal transduction pathway that is engaged by oligomeric (Aβ_o)to enhance presynaptic...

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...