Biology subjects

Grant, S. G.

Publications and source records attributed to Grant, S. G..

3 recordsLinked to original sources

bioRxiv2026

Region- and layer-specific glutamatergic synapse development in the nascent cortical hierarchy

Neocortical synapses are highly dynamic during brain development, undergoing formation, elimination, and maturation before acquiring properties that support adult cognition. Individual neocortical regions develop at different ages and individual layers within these regions contain distinct neuronal subtypes that process unique patterns of local and long-range synaptic input. To better understand the development of the cortical hierarchy we explored the laminar maturation of glutamatergic synapses across cortical regions. Synapse maturation was associated with the upregulation of the postsynaptic density protein PSD95. This maturation occurred in a region- and layer-specific manner -- layers associated with feedforward pathways develop earlier, while layers associated with higher-order circuits develop later. Our findings highlight adolescence as an important period for the cortex-wide maturation of synapses in cortical layer 1, synapses known to receive top-down feedback from higher-order cortices. We propose that this delayed adolescent maturation of top-down input represents a global signature of cortical development and seemingly acts as the final stage of outside-in brain maturation.

neuroscience↗

bioRxiv2021

Selective Vulnerability of Tripartite Synapses in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS.

neuroscience↗

bioRxiv2020

Estimation of the number of synapses in the hippocampus and brain-wide by volume electron microscopy and genetic labeling

Determining the number of synapses that are present in different brain regions is crucial to understand brain connectivity as a whole. Membrane-associated guanylate kinases (MAGUKs) are a family of scaffolding proteins that are expressed in excitatory glutamatergic synapses. We used genetic labeling of two of these proteins (PSD95 and SAP102), and Spinning Disc confocal Microscopy (SDM), to estimate the number of fluorescent puncta in the CA1 area of the hippocampus. We also used FIB-SEM, a three-dimensional electron microscopy technique, to calculate the actual numbers of synapses in the same area. We then estimated the ratio between the three-dimensional densities obtained with FIB-SEM (synapses/m3) and the bi-dimensional densities obtained with SDM (puncta/100 m2). Given that it is impractical to use FIB-SEM brain-wide, we used previously available SDM data from other brain regions and we applied this ratio as a conversion factor to estimate the minimum density of synapses in those regions. We found the highest densities of synapses in the isocortex, olfactory areas, hippocampal formation and cortical subplate. Low densities were found in the pallidum, hypothalamus, brainstem and cerebellum. Finally, the striatum and thalamus showed a wide range of synapse densities.

neuroscience↗