Biology subjects

Blockus, H.

Publications and source records attributed to Blockus, H..

4 recordsLinked to original sources

bioRxiv2022

Preconfigured dynamics in the hippocampus are guided by embryonic birthdate and rate of neurogenesis

The incorporation of novel information into the hippocampal network is likely be constrained by its innate architecture and internally generated activity patterns. However, the origin, organization, and consequences of such patterns remain poorly understood. Here, we show that hippocampal network dynamics are affected by sequential neurogenesis. We birthdated CA1 pyramidal neurons with in-utero electroporation over 4 embryonic days encompassing the peak of hippocampal neurogenesis, and compared their functional features in freely moving, adult mice. Neurons of the same birthdate displayed distinct connectivity, coactivity across brain states, and assembly dynamics. Same birthdate hippocampal neurons were topographically organized, in that anatomically clustered (<500{micro}m) neurons exhibited overlapping spatial representations. Overall, the wiring and functional features of CA1 pyramidal neurons reflected a combination of birthdate and the rate of neurogenesis. These observations demonstrate that sequential neurogenesis in embryonic development shapes the preconfigured forms of adult network dynamics.

neuroscience↗

bioRxiv2021

Compartment-specific tuning of hippocampal dendritic feature selectivity by intracellular Ca2+ release

Dendritic Ca2+ signaling is central to neural plasticity mechanisms allowing animals to adapt to the environment. Intracellular Ca2+ release (ICR) from endoplasmic reticulum has long been thought to shape these mechanisms. However, ICR has not been investigated in mammalian neurons in vivo. We combined electroporation of single CA1 pyramidal neurons, simultaneous imaging of dendritic and somatic activity during spatial navigation, optogenetic place field induction, and acute genetic augmentation of ICR cytosolic impact to reveal that ICR supports the establishment of dendritic feature selectivity and shapes integrative properties determining output-level receptive fields. This role for ICR was more prominent in apical than in basal dendrites. Thus, ICR cooperates with circuit-level architecture in vivo to promote the emergence of behaviorally-relevant plasticity in a compartment-specific manner.

neuroscience↗

bioRxiv2019

Synaptogenic activity of the axon guidance molecule Robo2 is critical for hippocampal circuit function

The developmental transition between axon guidance and synapse formation is critical for circuit assembly but still poorly understood at the molecular level. We hypothesized that this key transition could be regulated by axon guidance cues switching their function to regulate synaptogenesis with subcellular specificity. Here, we report evidence for such a functional switch, describing a novel role for the axon guidance molecule Robo2 in excitatory synapse formation onto dendrites of CA1 pyramidal neurons (PNs) in the mouse hippocampus. Cell-autonomous deletion of Robo2 from CA1 PNs leads to a drastic reduction of the number of excitatory synapses specifically in proximal dendritic compartments. At the molecular level, we show that this novel postsynaptic function of Robo2 depends on both its canonical ligand Slit and a novel interaction with presynaptic Neurexins. Biophysical analysis reveals that Robo2 binds directly to Neurexins via its Ig4-5 domains. In vivo 2-photon Ca2+ imaging of CA1 PNs during spatial navigation in mice shows that sparse deletion of Robo2 during development drastically reduces the likelihood of place cell emergence and alters spatial coding properties of the remaining place cells. Our results identify Robo2 as a novel molecular effector linking synaptic specificity to the acquisition of spatial coding properties characterizing hippocampal circuits.

neuroscience↗

bioRxiv2019

Activity-dependent nucleation of dynamic microtubules at presynaptic boutons is required for neurotransmission

Control of microtubule (MT) dynamics is critical for neuronal function. Whether MT nucleation is regulated at presynaptic boutons and influences overall presynaptic activity remains unknown. By visualizing MT dynamics at individual excitatory en passant boutons in axons of hippocampal neurons we found that MTs preferentially grow from presynaptic boutons as a result of {gamma}-tubulin and augmin-dependent nucleation. MT nucleation at boutons is promoted by neuronal activity, functionally coupled to synaptic vesicle (SV) transport, and required for neurotransmission. Hence, en passant boutons act as hotspots for activity-dependent MT nucleation, which is required for neurotransmission by providing the tracks for a rate-limiting supply of SVs to sites of neurotransmitter release.\n\nHighlightsO_LIExcitatory boutons are hotspots for neuronal activity-induced {gamma}-tubulin dependent MT nucleation\nC_LIO_LIThe augmin complex is required for the correct polarity of presynaptic de novo nucleated MTs\nC_LIO_LIPresynaptic MT nucleation promotes SV motility and exocytosis at sites of release\nC_LI\n\nIn BriefOur results demonstrate that excitatory en passant boutons are hotspots for neuronal activity-induced {gamma}-tubulin- and augmin-dependent oriented MT nucleation, and that the resulting presynaptic de novo nucleated MTs promote inter-bouton SV motility which is rate-limiting for neurotransmitter release.

cell biology↗