How Astrocytes Promote Hippocampal Inhibitory Circuit Development
Samantha Sutley-Koury, Christopher Taitano-Johnson, Anna Kulinich, Nadia Farooq, Victoria Wagner et al.
(see article e0154242024)
Epilepsy and autism spectrum disorders are characterized by hyperactive neurons. A known mechanism for neuronal hyperactivity is impaired inhibitory synapse development, which reduces the inhibition of excitatory neurons to drive their hyperactivity. Sutley-Koury et al. explored a mechanism underlying the development of inhibitory synapses in the mouse hippocampus that may be impaired in epilepsy and autism spectrum disorders. The authors previously discovered that astrocytic ephrin-B1 promotes the formation of inhibitory synapses onto hippocampal excitatory pyramidal neurons. Herein, they advance this finding by assessing the role of astrocytic ephrin-B1 in connectivity between inhibitory parvalbumin (PV) neurons and pyramidal neurons and by identifying another receptor involved in the mechanism.
Sutley-Koury et al. found that in the absence of ephrin-B1, there was a reduction of inhibition as well as increased seizure susceptibility and expression of a phenotype for autism spectrum disorders in mice. Downstream of ephrin-B1, the authors also discovered a new role for the EphB2 receptor, which is strongly implicated in the pathogenesis of autism spectrum disorders, in synapse development between inhibitory PV neurons and excitatory pyramidal hippocampal neurons. This work uncovers a new mechanism for how astrocytes promote synapse development between PV and pyramidal neurons, which may inform neurodevelopmental disorder treatment strategies.
Confocal images of control (top) and knock-out (bottom) mice showing VGAT (red) and gephyrin (green) immunostaining on excitatory pyramidal neurons labeled with GFP (blue). See Sutley-Koury et al. for more information.
Subcortical Involvement in High-Order Processing of Movements
Rhys Yewbrey and Katja Kornysheva
(see article e0832242024)
Cortical and subcortical motor networks have long been associated with learning and controlling motor skills. However, the role of the hippocampus in the performance of skilled fine motor behaviors, such as handwriting, typing, or playing an instrument, is less understood. A new study by Yewbrey and Kornysheva highlights the role of the hippocampus, a brain region traditionally linked to episodic memory and spatial navigation, in controlling skilled movements. The researchers used fMRI as study participants performed finger press sequences from memory and discovered that the hippocampus has a distributed pattern of activity reflecting information about the order of upcoming action sequences. In other words, the hippocampus seems to play a role in high-order processing by organizing action sequences so that movements can be efficiently executed. This expands the hippocampus's role in movement and procedural memory beyond episodic memory and may help point to new treatment targets for neurodegenerative disorders and motor skill deficits.
Footnotes
This Week in The Journal was written by Paige McKeon
