Dr Karolina Farrell

Genetic therapies for neurological diseases Often, gene therapy reviews concentrate upon specific therapeutic modalities – particularly either viral vector-mediated or a non-viral approach. Here, we draw together a comprehensive array of knowle...

Sorry all, been a bit away from social media - but very happy to show our latest, slightly massive review on neuro gene therapy. Some quite amazing co-authors who dwarf me in their amazingness. Here, as a pre-proof. Still some (quite a bit) of finessing pharmrev.aspetjournals.org/article/S003... 🧪

UCL – University College London UCL is consistently ranked as one of the top ten universities in the world (QS World University Rankings 2010-2022) and is No.2 in the UK for research power (Research Excellence Framework 2021).

Post doc job alert 📢! Announcing a v exciting job on a Wellcome-funded project in my group at UCL, looking at auditory hallucinations... Advert here 👀: rb.gy/230w8l - deadline is end of Oct. Please apply! 1/5

UCL – University College London UCL is consistently ranked as one of the top ten universities in the world (QS World University Rankings 2010-2022) and is No.2 in the UK for research power (Research Excellence Framework 2021).

New #job alert! Clinical research fellow / postdoc in #computationalpsychiatry at the @mpc-comppsych.bsky.social / @uclqsion.bsky.social and UCL psychiatry. We will aim to understand the computations engaged by serotonin in the treatment of depression. Please re-sky. www.ucl.ac.uk/work-at-ucl/...

We have a PhD project here, along with many other cool projects:

"Characterising and predicting seizure onsets from longitudinal sEEG data",
www.crick.ac.uk/careers-and-...

with @flor-iacaruso.bsky.social (Crick), Torsten Baldeweg (UCL) and Martin Tisdall (UCL).

Apply by: 14 November 2025.

Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories - Nature Communications The roles of distinct dopaminergic neuron subpopulations and the circuit projections driving their activity during threat behaviors remain incompletely understood. Here, the authors demonstrate that substantia nigra pars lateralis dopamine neurons receive selective, robust excitation from auditory and temporal association cortices, which, combined with rapid action potential firing, contributes to auditory threat conditioning.

Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories
www.nature.com/articles/s41...

Phenomenal. In my 10 year update of A Brief History, I make the point that in the first edition, not one disease had been successfully treated using gene therapy. Today that number is at least 7.

Individual differences in decision-making shape how mesolimbic dopamine regulates choice confidence and change-of-mind - Nature Neuroscience Differences in neuroeconomic decision-making influence nucleus accumbens dopamine dynamics and reflect choice confidence during evaluation, as well as past and future value during re-evaluation, which...

Nature Neuroscience

Individual differences in decision-making shape how mesolimbic dopamine regulates choice confidence and change-of-mind

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

Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant - Neuropsychopharmacology Neuropsychopharmacology - Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant

Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant
www.nature.com/articles/s41...

Disruption of hippocampal-prefrontal neural dynamics and risky decision-making in a mouse model of Alzheimer’s disease Kim et al. show that 5XFAD mice exhibit persistent risk-taking and reduced behavioral flexibility in naturalistic “approach food-avoid predator” foraging paradigms. Simultaneous neural recordings reve...

This paper has everything:
- a predator avoidance task with an eagle puppet 🦅
- rigid place coding and behavior in an #Alzheimer's model
- another predator avoidance task, with a taxidermied weasel 👀

Run, don't walk, to read one of my favorite papers this year: www.cell.com/cell-reports...

Flexible updating of reward and punishment contingencies by VTA GABA neurons In dynamic environments where stimuli predicting reward or punishment unexpectedly change, it is critical to flexibly update behavior while preserving…

New lab paper by @merridee.bsky.social identifying a novel role for VTA GABA neurons in behavioral flexibility

GABA, but not dopamine, neuron activation correlates with behavior when cues unexpectedly shift from predicting punishment to predicting reward www.sciencedirect.com/science/arti...

Cell-type-directed network-correcting combination therapy for Alzheimer’s disease A multi-cell-type drug discovery strategy targeting dysregulated gene networks in neurons and glia identified letrozole and irinotecan as a combination therapy that significantly improved memory and r...

The potential for 2 cancer drugs in combination to impact Alzheimer's disease as an outgrowth or single-cell RNA -seq, review of electronic health records from 1.4 million patients, and whittling down 1,300 potential repurposed drugs to 2.
www.cell.com/cell/fulltex...

Burnout is clinically understood as a combo of 6 factors—work overload, lack of control, insufficient rewards, breakdown in community, absence of fairness, & value conflicts—and only a fraction of it is under your control. Burnout is a systemic problem, so be kind to yourself and hard on the system.

Our work, out at Cell, shows that the brain’s dopamine signals teach each individual a unique learning trajectory. Collaborative experiment-theory effort, led by Sam Liebana in the lab. The first experiment my lab started just shy of 6y ago & v excited to see it out: www.cell.com/cell/fulltex...

Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression: a pooled participant analysis of randomized controlled trials Background Racemic ketamine and its enantiomer, esketamine, have emerged as fast-acting antidepressant options for individuals with treatment-resistant depression (TRD). Yet, despite growing clinical ...

🧠💥 Our new preprint is out!

We pooled 5 RCTs on intranasal esketamine for treatment-resistant depression—and found clear sex-specific patterns in how patients respond.
Read it here: www.medrxiv.org/content/10.1...

#TRD #Esketamine #Neuropsychiatry #OpenScience #MentalHealth

A mouse brain stereotaxic topographic atlas with isotropic 1-μm resolution - Nature A stereotaxic atlas of the whole mouse brain, based on a Nissl-stained cytoarchitecture dataset with isotropic 1-μm resolution, achieved through continuous micro-optical sectioning tomography, promise...

A mouse brain stereotaxic topographic atlas with isotropic 1-μm resolution
www.nature.com/articles/s41...

The Copilot Delusion Disclaimer: This post was written May 2025, and the arguments apply to AI code capabilities at this time. The arguments around lack of competence are certainly likely to become less prevalent-while th...

"When you outsource the thinking, you outsource the learning." deplet.ing/the-copilot-...

Event structure sculpts neural population dynamics in the lateral entorhinal cortex Our experience of the world is a continuous stream of events that must be segmented and organized at multiple timescales. The neural mechanisms underlying this process remain unknown. In this work, we...

Your brain doesn’t just passively track time ⏳ - it structures it.
In @Science.org we show that activity in 🧠 memory circuits (LEC) drifts constantly, but makes sharp jumps at key moments, segmenting life into meaningful events. (1/2)

👉 www.science.org/doi/10.1126/...

Mapping the projectional architecture of the mouse midbrain dopaminergic system using cell type-specific barcoding Brain-wide neural circuits are formed by the diverse axonal branching patterns of many individual neurons. Here we introduce POINTseq (projections of interest by sequencing), a high-throughput and use...

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

📌

The interoceptive origin of reinforcement learning Rewards play a crucial role in sculpting all motivated behavior. Traditionally, research on reinforcement learning has centered on how rewards guide learning and decision-making. Here, we examine the ...

The interoceptive origin of reinforcement learning www.cell.com/trends/cogni...

Overnight circuit remodelling drives juvenile alloparental care https://www.biorxiv.org/content/10.1101/2025.06.13.659524v1

Sex‐Specific Adaptations to VTA Circuits Following Subchronic Stress Subchronic variable stress, a paradigm shown to have divergent behavioral effects in males and females, induces shared and distinct physiological adaptations in the VTA. While both males and females ...

New work from my lab looking at how dopamine neurons are affected by stress and males and females! This paper comes to you through three rounds of major building construction, a pandemic, six months that we could not get TTX, some animal facility shenanigans and now is here on your internet!

A flexible hippocampal population code for experience relative to reward - Nature Neuroscience Sosa et al. find that hippocampal neural activity in mice encodes both environmental location and experience relative to rewards, spanning distances far from reward, through parallel and flexible popu...

It's officially published!! In my main postdoc work with @markplitt.bsky.social and @lgiocomo.bsky.social, we found that the hippocampus simultaneously encodes an animal's spatial position and its experience relative to reward in parallel population codes. 🧵

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

System-wide dissociation of reward and aversive dopaminergic signals Dopamine is central to reinforcement learning, classically linked to reward prediction error signaling. However, recent findings suggest a more complex picture, with dopamine neurons responding to ave...

First pre-print from the lab: www.biorxiv.org/content/10.1...

Conserved brain-wide emergence of emotional response from sensory experience in humans and mice Emotional responses to sensory experience are central to the human condition in health and disease. We hypothesized that principles governing the emergence of emotion from sensation might be discovera...

Conserved brain-wide emergence of emotional response from sensory experience in humans and mice
www.science.org/doi/10.1126/...

A computational approach to evaluate how molecular mechanisms impact large-scale brain activity - Nature Computational Science A computational framework is introduced to study how molecular changes impact brain activity, using biophysically grounded mean-field models to evaluate how drugs acting on synaptic receptors lead to ...

📢Alain Destexhe and colleagues from @neuropsi.bsky.social introduce a computational framework to study how molecular changes impact brain activity. #compneurosky #Neuroskyence www.nature.com/articles/s43...

Behavioral, computational and self-reported measures of reward and punishment sensitivity as predictors of mental health characteristics - Nature Mental Health Reinforcement learning task-based behavioral and computational measures displayed low test–retest reliability at the individual level. Also in contrast to self-assessed personality measures, behaviora...

nature.com/articles/s44220-025-00427-1
a challenging paper for computational psychiatry by @stepalminteri.bsky.social @mael-lebreton.bsky.social, but it's luckily not just a black/white picture with possibly state being better captured by behavioral tasks vs trait by self-reported questionnaires

Why animal models are useful for CNS drug discovery: Part 1 CNS drug discovery is more successful than oncology!!

Why are animal models useful for CNS drug discovery?

zendudest.substack.com/p/why-animal...

Error-driven changes in hippocampal representations accompany flexible re-learning https://www.biorxiv.org/content/10.1101/2025.05.20.655046v1

Systems consolidation reorganizes hippocampal engram circuitry Nature - A study shows that loss of memory precision associated with systems consolidation can be explained by neurogenesis-dependent reorganization of engram circuitry within the hippocampus over...

Sharing a new paper from the lab. This paper, led by Sangyoon Ko, represents a merging of two longstanding research themes in the lab-- adult neurogenesis and systems consolidation.

rdcu.be/el18q

A short thread follows for those interested.

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