Alessandro Gozzi
@gozziale.bsky.social
Senior scientist at Istituto Italiano di Tecnologia (Rovereto, Italy)
🧠 🐁 Functional Neuroimaging, Brain (dys)connectivity and Autism
ERC Grantee
www.gozzilab.it
🧠 🐁 Functional Neuroimaging, Brain (dys)connectivity and Autism
ERC Grantee
www.gozzilab.it
We tested this with a multivariate model (PLS) 📊 and found a prefrontal–dopaminergic network (VTA, NAcc) whose connectivity strongly predicts sociability in controls. Notably, this relationship breaks down in manipulated mice!
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September 10, 2025 at 3:08 PM
We tested this with a multivariate model (PLS) 📊 and found a prefrontal–dopaminergic network (VTA, NAcc) whose connectivity strongly predicts sociability in controls. Notably, this relationship breaks down in manipulated mice!
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We tested this hypothesis using spatial gene decoding of fMRI maps. 🧬We found that dysregulated genes were indeed highly expressed in social brain regions, but not in intact networks. 👉This may explain why early E:I imbalance may selectively disrupts social circuits!
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September 10, 2025 at 3:08 PM
We tested this hypothesis using spatial gene decoding of fMRI maps. 🧬We found that dysregulated genes were indeed highly expressed in social brain regions, but not in intact networks. 👉This may explain why early E:I imbalance may selectively disrupts social circuits!
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The fMRI results made total sense: we saw selective hypoconnectivity between PFC and social brain hubs (striatum, cingulate, limbic regions). Mirroring the behavior of these mice, sensory networks were instead intact. So connectivity disruption targets social circuits specifically!
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September 10, 2025 at 3:08 PM
The fMRI results made total sense: we saw selective hypoconnectivity between PFC and social brain hubs (striatum, cingulate, limbic regions). Mirroring the behavior of these mice, sensory networks were instead intact. So connectivity disruption targets social circuits specifically!
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This points to lasting cortical hyperexcitability as the driver of hypo-sociability! To test this hypothesys, we treated adult mice with R-baclofen or bumetanide (both dampen excitability) 💊 Remarkably, social deficits were reversed suggesting that persistent hyperexcitability drives behavior!
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September 10, 2025 at 3:08 PM
This points to lasting cortical hyperexcitability as the driver of hypo-sociability! To test this hypothesys, we treated adult mice with R-baclofen or bumetanide (both dampen excitability) 💊 Remarkably, social deficits were reversed suggesting that persistent hyperexcitability drives behavior!
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How do these changes play out at the neural population level? EEG in adult mice showed that early developmental E:I imbalance results in lasting cortical hyperexcitability
⚡Even more striking: we found an EEG “Hurst exponent” signature that mirrors what’s seen in autistic individuals
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⚡Even more striking: we found an EEG “Hurst exponent” signature that mirrors what’s seen in autistic individuals
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September 10, 2025 at 3:08 PM
How do these changes play out at the neural population level? EEG in adult mice showed that early developmental E:I imbalance results in lasting cortical hyperexcitability
⚡Even more striking: we found an EEG “Hurst exponent” signature that mirrors what’s seen in autistic individuals
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⚡Even more striking: we found an EEG “Hurst exponent” signature that mirrors what’s seen in autistic individuals
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But how do these behavioral changes arise? We first investigated whether alterations in synaptic genes would affect electric properties of neurons. Patch-clamp studies showed this this is actually the case
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September 10, 2025 at 3:08 PM
But how do these behavioral changes arise? We first investigated whether alterations in synaptic genes would affect electric properties of neurons. Patch-clamp studies showed this this is actually the case
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Notably, we found lasting dysregulation of 530 genes 🧬, many of which are known synaptic-related autism risk genes! Moreover, dysregulated genes overlapped with autism postmortem transcriptional data🧠.
This suggests that what we investigate here could be directly relevant to autism!
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This suggests that what we investigate here could be directly relevant to autism!
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September 10, 2025 at 3:08 PM
Notably, we found lasting dysregulation of 530 genes 🧬, many of which are known synaptic-related autism risk genes! Moreover, dysregulated genes overlapped with autism postmortem transcriptional data🧠.
This suggests that what we investigate here could be directly relevant to autism!
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This suggests that what we investigate here could be directly relevant to autism!
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We thought: maybe heightened neuronal activity doesn’t just fade away. Maybe it reprograms the transcriptome through activity-dependent mechanisms.
If so, manipulated mice should show a signature of transcriptional reprogramming. We thus tested this using RNAseq in cortex of manipulated mice
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If so, manipulated mice should show a signature of transcriptional reprogramming. We thus tested this using RNAseq in cortex of manipulated mice
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September 10, 2025 at 3:08 PM
We thought: maybe heightened neuronal activity doesn’t just fade away. Maybe it reprograms the transcriptome through activity-dependent mechanisms.
If so, manipulated mice should show a signature of transcriptional reprogramming. We thus tested this using RNAseq in cortex of manipulated mice
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If so, manipulated mice should show a signature of transcriptional reprogramming. We thus tested this using RNAseq in cortex of manipulated mice
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Importantly, we do not see behavioral changes if this manipulation is applied in adolescence. This confirms our critical window and strengthens (just a bit..) the (at this point still weak) possible link to autism..
But what could be driving these social deficits?
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But what could be driving these social deficits?
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September 10, 2025 at 3:08 PM
Importantly, we do not see behavioral changes if this manipulation is applied in adolescence. This confirms our critical window and strengthens (just a bit..) the (at this point still weak) possible link to autism..
But what could be driving these social deficits?
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But what could be driving these social deficits?
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But does developmental E:I imbalance affect mouse behavior? Yes it does! Manipulated mice 🐭show persistent ("autism-like") social deficits (replicated with different tests) but (rathersurprisingly) no major motor, sensory, olfactory, memory issues
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September 10, 2025 at 3:08 PM
But does developmental E:I imbalance affect mouse behavior? Yes it does! Manipulated mice 🐭show persistent ("autism-like") social deficits (replicated with different tests) but (rathersurprisingly) no major motor, sensory, olfactory, memory issues
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We designed a chemogenetic strategy 🔬 to transiently boost excitability in neocortical (Vglut1+) pyramidal neurons of newborn mice (P1-P14)
Control studies showed that this manipulation transiently increases neuronal excitability (without causing epilepsy). So far so good!
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Control studies showed that this manipulation transiently increases neuronal excitability (without causing epilepsy). So far so good!
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September 10, 2025 at 3:08 PM
We designed a chemogenetic strategy 🔬 to transiently boost excitability in neocortical (Vglut1+) pyramidal neurons of newborn mice (P1-P14)
Control studies showed that this manipulation transiently increases neuronal excitability (without causing epilepsy). So far so good!
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Control studies showed that this manipulation transiently increases neuronal excitability (without causing epilepsy). So far so good!
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We thought, maybe the answer lies in development:
a short-lived imbalance during a critical early window might permanently derail circuit formation and produce autism-relevant phenotypes.
And this is precisely the hypothesis we set out to test in mice!
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a short-lived imbalance during a critical early window might permanently derail circuit formation and produce autism-relevant phenotypes.
And this is precisely the hypothesis we set out to test in mice!
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September 10, 2025 at 3:08 PM
We thought, maybe the answer lies in development:
a short-lived imbalance during a critical early window might permanently derail circuit formation and produce autism-relevant phenotypes.
And this is precisely the hypothesis we set out to test in mice!
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a short-lived imbalance during a critical early window might permanently derail circuit formation and produce autism-relevant phenotypes.
And this is precisely the hypothesis we set out to test in mice!
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The E:I imbalance theory for autism posits that too much excitation or too little inhibition destabilize cortical circuits⚡ leading to hyperexcitability & autism-related dysfunction
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September 10, 2025 at 3:08 PM
The E:I imbalance theory for autism posits that too much excitation or too little inhibition destabilize cortical circuits⚡ leading to hyperexcitability & autism-related dysfunction
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🚨 Excited to share the latest preprint form the lab ➡️https://tinyurl.com/32d3be9f
Here we tackle a long-standing chicken-or-egg 🐣🥚question in #autism and developmental neuroscience
➡️ Is excitation–inhibition (E:I) imbalance a "cause" or a "consequence" of #autism?
Check out what we found!
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Here we tackle a long-standing chicken-or-egg 🐣🥚question in #autism and developmental neuroscience
➡️ Is excitation–inhibition (E:I) imbalance a "cause" or a "consequence" of #autism?
Check out what we found!
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September 10, 2025 at 3:08 PM
This looks pretty cool: ultrasound can now see through the skull! 🧠🔊
The skull has long been a barrier to ultrasound. This reprint shows how to make it quickly transparent → enabling full-depth, high-res fUSI in mice (& humans! 🤯🤯)
Huge congrats to the authors!!!
www.biorxiv.org/content/10.1...
The skull has long been a barrier to ultrasound. This reprint shows how to make it quickly transparent → enabling full-depth, high-res fUSI in mice (& humans! 🤯🤯)
Huge congrats to the authors!!!
www.biorxiv.org/content/10.1...
September 3, 2025 at 1:35 PM
This looks pretty cool: ultrasound can now see through the skull! 🧠🔊
The skull has long been a barrier to ultrasound. This reprint shows how to make it quickly transparent → enabling full-depth, high-res fUSI in mice (& humans! 🤯🤯)
Huge congrats to the authors!!!
www.biorxiv.org/content/10.1...
The skull has long been a barrier to ultrasound. This reprint shows how to make it quickly transparent → enabling full-depth, high-res fUSI in mice (& humans! 🤯🤯)
Huge congrats to the authors!!!
www.biorxiv.org/content/10.1...
🧠✨Giving a keynote at #OHBM2025 has been one of the greatest honors of my career!
Deeply grateful to this outstanding community for its openness, curiosity & for welcoming outsiders like me with such warmth and generosity💙
I’ll carry the memories of this experience with me for a long, long time!
Deeply grateful to this outstanding community for its openness, curiosity & for welcoming outsiders like me with such warmth and generosity💙
I’ll carry the memories of this experience with me for a long, long time!
June 27, 2025 at 9:52 AM
🧠✨Giving a keynote at #OHBM2025 has been one of the greatest honors of my career!
Deeply grateful to this outstanding community for its openness, curiosity & for welcoming outsiders like me with such warmth and generosity💙
I’ll carry the memories of this experience with me for a long, long time!
Deeply grateful to this outstanding community for its openness, curiosity & for welcoming outsiders like me with such warmth and generosity💙
I’ll carry the memories of this experience with me for a long, long time!
2️⃣ On Thursday morning (symposium #1166) @edeguz.bsky.social will instead discuss how optogenetically-induced brain oscillations can help uncover the neural rhythms that causally support fMRI connectivity. Spoiler: when it comes to fMRI connectivity, the slower, the better!
See you all in Brisbane!
See you all in Brisbane!
June 23, 2025 at 12:25 PM
2️⃣ On Thursday morning (symposium #1166) @edeguz.bsky.social will instead discuss how optogenetically-induced brain oscillations can help uncover the neural rhythms that causally support fMRI connectivity. Spoiler: when it comes to fMRI connectivity, the slower, the better!
See you all in Brisbane!
See you all in Brisbane!
Excited to reconnect with #OHBM2025 community! This year my lab will be presenting two different studies
1️⃣ In poster presentation #1311, we will show how a brief and transient developmental Excitation/Inhibition imbalance may irreversibly disrupt cortical fMRI connectivity. How? Epigenetics is key!
1️⃣ In poster presentation #1311, we will show how a brief and transient developmental Excitation/Inhibition imbalance may irreversibly disrupt cortical fMRI connectivity. How? Epigenetics is key!
June 23, 2025 at 12:25 PM
Excited to reconnect with #OHBM2025 community! This year my lab will be presenting two different studies
1️⃣ In poster presentation #1311, we will show how a brief and transient developmental Excitation/Inhibition imbalance may irreversibly disrupt cortical fMRI connectivity. How? Epigenetics is key!
1️⃣ In poster presentation #1311, we will show how a brief and transient developmental Excitation/Inhibition imbalance may irreversibly disrupt cortical fMRI connectivity. How? Epigenetics is key!
Two years after a fun and inspiring retreat at our institute in #Rovereto, our position paper on the future of rodent functional neuroimaging is finally out 🐭🧠👇
📄https://tinyurl.com/42spkbft
Here we outline key challenges & a roadmap to advance the field! Proud of this collaborative effort 🥳🎉
📄https://tinyurl.com/42spkbft
Here we outline key challenges & a roadmap to advance the field! Proud of this collaborative effort 🥳🎉
May 26, 2025 at 2:49 PM
Two years after a fun and inspiring retreat at our institute in #Rovereto, our position paper on the future of rodent functional neuroimaging is finally out 🐭🧠👇
📄https://tinyurl.com/42spkbft
Here we outline key challenges & a roadmap to advance the field! Proud of this collaborative effort 🥳🎉
📄https://tinyurl.com/42spkbft
Here we outline key challenges & a roadmap to advance the field! Proud of this collaborative effort 🥳🎉
🎓 My lab has 2 PhD positions with @cimecunitrento.bsky.social
1️⃣ 🧠 Watch the 🐭 brain in motion, with functional ultrasound imaging (fUSI)
2️⃣🧪 Mess with the 🐭 brain (experimentally) via causal perturbations + imaging
🔬 Neuro/physics/bioengeneering backgrounds welcome
👉Info ▶️https://lnkd.in/dDeTTDj2
1️⃣ 🧠 Watch the 🐭 brain in motion, with functional ultrasound imaging (fUSI)
2️⃣🧪 Mess with the 🐭 brain (experimentally) via causal perturbations + imaging
🔬 Neuro/physics/bioengeneering backgrounds welcome
👉Info ▶️https://lnkd.in/dDeTTDj2
May 6, 2025 at 3:29 PM
🎓 My lab has 2 PhD positions with @cimecunitrento.bsky.social
1️⃣ 🧠 Watch the 🐭 brain in motion, with functional ultrasound imaging (fUSI)
2️⃣🧪 Mess with the 🐭 brain (experimentally) via causal perturbations + imaging
🔬 Neuro/physics/bioengeneering backgrounds welcome
👉Info ▶️https://lnkd.in/dDeTTDj2
1️⃣ 🧠 Watch the 🐭 brain in motion, with functional ultrasound imaging (fUSI)
2️⃣🧪 Mess with the 🐭 brain (experimentally) via causal perturbations + imaging
🔬 Neuro/physics/bioengeneering backgrounds welcome
👉Info ▶️https://lnkd.in/dDeTTDj2
If this was the case, we would expect a positive association between fMRI and autism-relevant scores (e.g., SRS) in childhood, reverting to a negative one after puberty. We actually found evidence of such relationship in somatosensory areas of 22q11DS individuals!
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March 13, 2025 at 2:42 PM
If this was the case, we would expect a positive association between fMRI and autism-relevant scores (e.g., SRS) in childhood, reverting to a negative one after puberty. We actually found evidence of such relationship in somatosensory areas of 22q11DS individuals!
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We finally asked what could be the behavioral significance of these observations. Gene decoding revealed a disproportionately-high enrichment for autism-related genes in the affected cortical areas.
We thus hypothesized that this phenomenon could be associated with autism-relevant symptoms
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We thus hypothesized that this phenomenon could be associated with autism-relevant symptoms
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March 13, 2025 at 2:42 PM
We finally asked what could be the behavioral significance of these observations. Gene decoding revealed a disproportionately-high enrichment for autism-related genes in the affected cortical areas.
We thus hypothesized that this phenomenon could be associated with autism-relevant symptoms
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We thus hypothesized that this phenomenon could be associated with autism-relevant symptoms
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We found this to be the case! GSK3β-related synaptic mechanisms may thus underlie the observed dysconnectivity in 22q11DS
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March 13, 2025 at 2:42 PM
We found this to be the case! GSK3β-related synaptic mechanisms may thus underlie the observed dysconnectivity in 22q11DS
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Are analogous synaptic mechanisms implicated in human 22q11DS dysconnectivity?
To test this, we used gene decoding analyses to investigate if brain regions exhibiting developmental dysconnectivity would be specifically enriched for synaptic-relevant GSK3β‐interactors
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To test this, we used gene decoding analyses to investigate if brain regions exhibiting developmental dysconnectivity would be specifically enriched for synaptic-relevant GSK3β‐interactors
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March 13, 2025 at 2:42 PM
Are analogous synaptic mechanisms implicated in human 22q11DS dysconnectivity?
To test this, we used gene decoding analyses to investigate if brain regions exhibiting developmental dysconnectivity would be specifically enriched for synaptic-relevant GSK3β‐interactors
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To test this, we used gene decoding analyses to investigate if brain regions exhibiting developmental dysconnectivity would be specifically enriched for synaptic-relevant GSK3β‐interactors
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Interestingly, we found that developmental inhibition of GSK3β activity (SB in the figure) robustly normalized both spine density *and* fMRI dysconnectivity in LgDel mice. This finding suggests that the two phenotypes may be causally linked to one another!
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March 13, 2025 at 2:42 PM
Interestingly, we found that developmental inhibition of GSK3β activity (SB in the figure) robustly normalized both spine density *and* fMRI dysconnectivity in LgDel mice. This finding suggests that the two phenotypes may be causally linked to one another!
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