Jacques Carolan
@jacquescarolan.bsky.social
Applied Physicist & Neuroscientist || Current: Programme Director @ ARIA || Previous: Neuroscience @ UCL & Quantum Computing @ MIT || He/Him
https://www.aria.org.uk
https://jacquescarolan.github.io
https://www.aria.org.uk
https://jacquescarolan.github.io
Finally: on a personal note this has been such a wild journey. I spent 10 years building quantum computers and then jacked it all in to try and become a neuroscientist (I don't have high-school biology lol). The reason I could do this is because of wonderful friends at the Neural Computation Lab!
October 6, 2025 at 10:52 AM
Finally: on a personal note this has been such a wild journey. I spent 10 years building quantum computers and then jacked it all in to try and become a neuroscientist (I don't have high-school biology lol). The reason I could do this is because of wonderful friends at the Neural Computation Lab!
Together, this is a blueprint for defining synaptic plasticity rules *during behaviour*, with direct voltage readout on standard 2-photon rigs. Check out the paper here: www.nature.com/articles/s41...
All-optical voltage interrogation for probing synaptic plasticity in vivo - Nature Communications
Reliable measuring the voltage dynamics of individual neurons in the intact brain is significantly challenging. Here authors developed an all-optical method combining two-photon voltage imaging and optogenetics to measure and induce synaptic plasticity in vivo, revealing LTP of inhibition in cerebellar circuits and providing a blueprint to link synaptic changes to learning.
www.nature.com
October 6, 2025 at 10:52 AM
Together, this is a blueprint for defining synaptic plasticity rules *during behaviour*, with direct voltage readout on standard 2-photon rigs. Check out the paper here: www.nature.com/articles/s41...
Finally, we used this to probe synaptic plasticity. Pairing climbing fibre input before granule cell activation induced potentiation of IPSPs, lasting at least 40 min. Smaller IPSPs potentiated more, and neighbours co-potentiated — revealing circuit-level learning rules.
October 6, 2025 at 10:52 AM
Finally, we used this to probe synaptic plasticity. Pairing climbing fibre input before granule cell activation induced potentiation of IPSPs, lasting at least 40 min. Smaller IPSPs potentiated more, and neighbours co-potentiated — revealing circuit-level learning rules.
Because we could image full dendritic arbors across multiple cells, we saw rich circuit dynamics: precise synchrony of CF-evoked events, spatially diverse inhibition across branches, and global vs local patterns of dendritic activity.
October 6, 2025 at 10:52 AM
Because we could image full dendritic arbors across multiple cells, we saw rich circuit dynamics: precise synchrony of CF-evoked events, spatially diverse inhibition across branches, and global vs local patterns of dendritic activity.
With this, we captured high-fidelity recordings of spontaneous and sensory-evoked complex spikes, optogenetically evoked IPSPs (via feedforward inhibition) + even the occasional EPSP!
October 6, 2025 at 10:52 AM
With this, we captured high-fidelity recordings of spontaneous and sensory-evoked complex spikes, optogenetically evoked IPSPs (via feedforward inhibition) + even the occasional EPSP!
We expressed JEDI-2Psub in Purkinje cell dendrites and opsins in cerebellar granule cells. This enables us to both image voltage at postsynaptic dendrites and precisely activate presynaptic inputs with light.
October 6, 2025 at 10:52 AM
We expressed JEDI-2Psub in Purkinje cell dendrites and opsins in cerebellar granule cells. This enables us to both image voltage at postsynaptic dendrites and precisely activate presynaptic inputs with light.
At the heart of this is a new voltage indicator — JEDI-2Psub — from colleagues at the St.Pierre Lab. Optimised for subthreshold signals, it gives ~3.5× larger responses near rest compared to JEDI-2P. This makes it ideal for capturing synaptic potentials.
October 6, 2025 at 10:52 AM
At the heart of this is a new voltage indicator — JEDI-2Psub — from colleagues at the St.Pierre Lab. Optimised for subthreshold signals, it gives ~3.5× larger responses near rest compared to JEDI-2P. This makes it ideal for capturing synaptic potentials.
That’s the vision we’re exploring.
If you’re working on transformative, unconventional ideas to 1000x the scale of neurotech or have answers to the following questions — I’d love to hear from you!
📖 Full post: link.aria.org.uk/jacquessubst...
If you’re working on transformative, unconventional ideas to 1000x the scale of neurotech or have answers to the following questions — I’d love to hear from you!
📖 Full post: link.aria.org.uk/jacquessubst...
August 29, 2025 at 12:57 PM
That’s the vision we’re exploring.
If you’re working on transformative, unconventional ideas to 1000x the scale of neurotech or have answers to the following questions — I’d love to hear from you!
📖 Full post: link.aria.org.uk/jacquessubst...
If you’re working on transformative, unconventional ideas to 1000x the scale of neurotech or have answers to the following questions — I’d love to hear from you!
📖 Full post: link.aria.org.uk/jacquessubst...
Neurotech needs the same inflection point.
From invasive, last-resort procedures → simple, scalable, globally accessible platforms.
The 1950s had the transistor. Today the convergence of engineered biology + hardware could make a surgery-free, platform neurotechnology possible
From invasive, last-resort procedures → simple, scalable, globally accessible platforms.
The 1950s had the transistor. Today the convergence of engineered biology + hardware could make a surgery-free, platform neurotechnology possible
August 29, 2025 at 12:57 PM
Neurotech needs the same inflection point.
From invasive, last-resort procedures → simple, scalable, globally accessible platforms.
The 1950s had the transistor. Today the convergence of engineered biology + hardware could make a surgery-free, platform neurotechnology possible
From invasive, last-resort procedures → simple, scalable, globally accessible platforms.
The 1950s had the transistor. Today the convergence of engineered biology + hardware could make a surgery-free, platform neurotechnology possible
I think cardiology in the 1950s is a great case study, where treating heart block required open-heart surgery.
The leap wasn’t “better surgery.”
It was the transvenous lead — a minimally invasive access route that unlocked millions of pacemaker implants/year. ❤️⚡
The leap wasn’t “better surgery.”
It was the transvenous lead — a minimally invasive access route that unlocked millions of pacemaker implants/year. ❤️⚡
August 29, 2025 at 12:57 PM
I think cardiology in the 1950s is a great case study, where treating heart block required open-heart surgery.
The leap wasn’t “better surgery.”
It was the transvenous lead — a minimally invasive access route that unlocked millions of pacemaker implants/year. ❤️⚡
The leap wasn’t “better surgery.”
It was the transvenous lead — a minimally invasive access route that unlocked millions of pacemaker implants/year. ❤️⚡
DBS for PD is a great proof point: effective, approved, reimbursed… yet only a fraction of people eligible receive it.
Complex surgery imposes a series of stacked, multiplicative barriers that fundamentally limit scalability.
So what do we do?
Complex surgery imposes a series of stacked, multiplicative barriers that fundamentally limit scalability.
So what do we do?
August 29, 2025 at 12:57 PM
DBS for PD is a great proof point: effective, approved, reimbursed… yet only a fraction of people eligible receive it.
Complex surgery imposes a series of stacked, multiplicative barriers that fundamentally limit scalability.
So what do we do?
Complex surgery imposes a series of stacked, multiplicative barriers that fundamentally limit scalability.
So what do we do?
Emerging therapies show real promise:
⚡ Targeted electrical stimulation for intractable psychiatric disorders
🧬 Cell therapies for neurodegenerative disease
But they won’t scale to the millions who need them.
doi.org/10.1016/j.br...
doi.org/10.1016/j.pa...
⚡ Targeted electrical stimulation for intractable psychiatric disorders
🧬 Cell therapies for neurodegenerative disease
But they won’t scale to the millions who need them.
doi.org/10.1016/j.br...
doi.org/10.1016/j.pa...
https://doi.org/10.1016/j.brs.2025.08.017
t.co
August 29, 2025 at 12:57 PM
Emerging therapies show real promise:
⚡ Targeted electrical stimulation for intractable psychiatric disorders
🧬 Cell therapies for neurodegenerative disease
But they won’t scale to the millions who need them.
doi.org/10.1016/j.br...
doi.org/10.1016/j.pa...
⚡ Targeted electrical stimulation for intractable psychiatric disorders
🧬 Cell therapies for neurodegenerative disease
But they won’t scale to the millions who need them.
doi.org/10.1016/j.br...
doi.org/10.1016/j.pa...
We’re facing a global brain-health crisis:
🧠 Brain disorders = biggest disease burden worldwide
💔 3× that of heart disease
💰 Costs US + Europe $1.7 trillion annually
And the gap between need & treatment is only widening.
doi.org/10.1159/0005...
🧠 Brain disorders = biggest disease burden worldwide
💔 3× that of heart disease
💰 Costs US + Europe $1.7 trillion annually
And the gap between need & treatment is only widening.
doi.org/10.1159/0005...
August 29, 2025 at 12:57 PM
We’re facing a global brain-health crisis:
🧠 Brain disorders = biggest disease burden worldwide
💔 3× that of heart disease
💰 Costs US + Europe $1.7 trillion annually
And the gap between need & treatment is only widening.
doi.org/10.1159/0005...
🧠 Brain disorders = biggest disease burden worldwide
💔 3× that of heart disease
💰 Costs US + Europe $1.7 trillion annually
And the gap between need & treatment is only widening.
doi.org/10.1159/0005...
March 12, 2025 at 2:33 PM
Love this. Definitely the cerebellum. Specifically how different cell types map onto specific components of an adaptive filter www.nature.com/articles/nrn...
January 27, 2025 at 1:24 PM
Love this. Definitely the cerebellum. Specifically how different cell types map onto specific components of an adaptive filter www.nature.com/articles/nrn...
Thanks for amplifying Susanne! Inspired by your awesome work over at Wellcome Leap.
January 20, 2025 at 5:21 PM
Thanks for amplifying Susanne! Inspired by your awesome work over at Wellcome Leap.