Amazing work by Max Wilson, Ania Sumera, and Emre Berk - with exceptional support from UK MRC @ukri.org, @sidb-edinburgh.bsky.social, and @edinunineuro.bsky.social

This raises the interesting question of how many single-cell phenotypes in this model are effectively compensated for to maintain network fidelity....

Frontiers | Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome IntroductionFragile X Syndrome is a common, inherited single gene cause of intellectual disability, associated with autism, epilepsy, anxiety, and sensory di...

We just published a thing!

www.frontiersin.org/journals/pha...

Here we show that somatostatin interneurons display exaggerated LTP in a mouse model of Fragile X Syndrome, and which is sensitive to GABAB receptor activation; but which are not manifested at the circuit level - more work to do!

New @who.int Global Status Report on Neurology calls for urgent action to address the growing burden of neurological disorders & to promote brain health for ALL. @arinatam.bsky.social co-authored Ch4: Effective, timely & responsive diagnosis, treatment & care. Full report:
edin.ac/43r3P7U

This work hopefully identifies new models of neurodevelopmental conditions which can revolutionise future research.

With insane support from @sidb-edinburgh.bsky.social @edinunineuro.bsky.social @ukri.org @patrickwildcentre.bsky.social

and help from @vectorbuilder.bsky.social

This work has been championed by Max Knops and @sorayam.bsky.social, and many other colleagues, not limited to: Max Wilson, @bonthronphd.bsky.social @l-w-taylor.bsky.social
Alsadeg Bilal, Imran Liaquat, Paul Brennan, @clairedurrant1.bsky.social

FMRP regulates adult human cortical excitability via cyclic-AMP signalling Fragile X Syndrome (FXS) is a common inherited neurodevelopmental condition, resulting from loss of Fragile X Messenger Ribonuclear Protein (FMRP). Rodent models of FXS display cellular hyperexcitabil...

www.biorxiv.org/content/10.1...

super excited to release this. nearly 7 years ago, we set out to investigate whether FMRP regulates excitability of neurons in living human brain tissue. we find loss of FMRP in adult neurons leads to elevated excitability, corrected by PDE4D inhibition.

This work was led by Ania Sumera and Laura Oliveira, but with help from immensely talented students and collaborators, and @edinunineuro.bsky.social @sidb-edinburgh.bsky.social

Despite an absence of AIS shortening in response to sustained activity modulation, we do see other functional changes associated with homeostatic plasticity - including changes in membrane excitability and NMDA receptor function

Hello world!
We just released a thing! In this preprint we provide evidence questioning the ability of the axon initial segment to undergo rapid structural plasticity in intact neurons from mouse, rat, and human cortex.

Scottish Neuroscience Initiative Takes Basic Science From Lab to Clinic The Simons Initiative for the Developing Brain aims to discover biological mechanisms underlying autism and related neurodevelopmental disorders and to use that information to deliver therapeutic…

Meet the Simons Initiative for the Developing Brain: a center devoted to deconstructing the secrets of neurodevelopmental disorders and the developing brain. Read more: annualreports.simonsfoundation.org/2024/scottis... #science #neuroscience

And amazing collaborators @clairedurrant1.bsky.social @sorayam.bsky.social @l-w-taylor.bsky.social among many others not on here :)

This work would not be possible without the patients, our funders @sidb-edinburgh.bsky.social, UK MRC, @edinunineuro.bsky.social

Finally, we show show that GABAB receptor currents are elevated in patients who receive the anti-seizure medication Levetiracetam - regardless of seizure history.

Further, we show that presynaptic GABAB receptors signalling is stronger in human cortical inputs than rodents. This leads to differential control of cortical oscillations.

In this we find that postsynaptoc GABAB receptors signalling undergoes developmental maturation in cortical columns, but is largely stable over adult human life.

Phylogenetic divergence of GABAB receptor signaling in neocortical networks over adult life - Nature Communications GABAB receptors contribute to complex inhibition that regulates cortical neurons in a translationally relevant manner over adult life. Here, authors show stronger presynaptic inhibition in humans than...

What, what! We just published our work studying GABAB receptors in human and rat brain.

www.nature.com/articles/s41...

Divergent actions of physiological and pathological amyloid-β on synapses in live human brain slice cultures Nature Communications - Understanding synapse loss in Alzheimer’s disease has been hampered by a lack of human model systems. Here, the authors show that manipulation of physiological or...

Our paper in Nature Comms is now online! Summary below but in short we use living human brain slice cultures in a number of different ways to model dementia processes. Big team effort led by myself, @robertmcgeachan.bsky.social and @clairedurrant1.bsky.social rdcu.be/ej647

Friday saw two momentous occasions. The first major study accepted from our lab 🥳 and my 5 year old reciting to me the principles of synaptic strengthening in learning and memory. Immensely proud of both...

True, but if many of the facets of microglial function have been attributed to their role in mouse brain circuits, then perhaps not all is as it seems. A conditional FIRE mouse or rat could/would approach an answer

That is an interesting point. That being said rats lacking the CSF1R gene survive pretty well... see Patkar et al 2021 ... But with some deficits in neuronal progenitors. More to do!

Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus - Nature Neuroscience Microglia are proposed to have a role in brain development through synaptic engulfment and paracrine signaling. O’Keeffe et al. show that certain neurodevelopmental processes attributed to microglia c...

We just published a thing!
In this study, we provide compelling evidence that a lack of microglia during early brain development does not lead to wholesale alterations of synaptic and cellular function.

www.nature.com/articles/s41...