Narayanan Lab

D1FLP mice are now available from JAX!
www.jax.org/strain/039507

Detailed in this paper: pubmed.ncbi.nlm.nih.gov/39701542/

Let us know if they work for you...

Linear predictive coding electroencephalography algorithms predict Parkinson's disease mortality using out-of-sample tests Background: Parkinson's disease (PD) increases mortality is difficult to predict because of its heterogeneity and the availability of very few reliable which prognostic markers. Objectives: We used el...

Our latest paper predicting PD mortality from ~2 minutes of resting-state EEG : www.medrxiv.org/content/10.1...

Timing, movement, and reward contributions to prefrontal and striatal ramping activity Across species, prefrontal and striatal neurons exhibit time-dependent ramping activity, defined as a consistent monotonic change in firing rate across temporal intervals. However, it is unclear if ra...

Our latest work: www.biorxiv.org/content/10.1...

We show that corticostriatal ramping activity can't readily be explained by movements using motion tracking, and that ramping can't readily be explained by reward anticipation in mice performing timing and Pavlovian tasks.

Our work from a great collaboration now out at Brain Stimulation: doi.org/10.1016/j.br...

We find that 4 Hz STN stimulation in *humans* changes decision thresholds:

Data: narayanan.lab.uiowa.edu and osf.io/hsz3u
With Rachel Cole and Jim Cavanagh

Our work from a great collaboration now out at Brain Stimulation: doi.org/10.1016/j.br...

We find that 4 Hz STN stimulation in *humans* changes decision thresholds:

Data: narayanan.lab.uiowa.edu and osf.io/hsz3u

Amphetamine scrambles the brain's sense of time by degrading prefrontal neuron coordination Researchers have found that amphetamine alters how the brain processes time, increasing variability in the activity of neurons that encode temporal information. The study provides insight into how the...

write-up of our amphetamine paper: www.psypost.org/amphetamine-...

another new preprint from our group on predicting cognitive changes in PD from resting state fMRI: medrxiv.org/content/10.1...

Diverse activity in prefrontal projections promotes temporal control of action Prefrontal neurons can have diverse activity during cognitive functions like working memory, attention, and timing; however, the importance of this heterogeneity is unclear. Our goal was to better und...

Our latest preprint on projection-specific tracing of prefrontal activity: www.biorxiv.org/cgi/content/...

Lots more details in the paper. This paper challenged our fundamental view of what we think amphetamine does…

Amphetamine has been thought to reliably affect timing accuracy. We find in a meta-analysis and in our data that it actually more reliably affects precision:

Our work showing that amphetamine affects behavior by degrading prefrontal temporal variability is now out at Neuropharmacology: doi.org/10.1016/j.ne...

Work by Matthew Weber and colleagues:

As always, data and code at: narayanan.lab.uiowa.edu/datasets

That's us!

New preprint from our group showing that drugs that enhance glycolysis slow neurodegeneration in Alzheimer's disease - data from yeast to humans:
www.biorxiv.org/content/10.1...
data: bit.ly/GlycolysisANDAD
Data and code : narayanan.lab.uiowa.edu/home/data

Congrats - awesome work - George A would have read this with interest!

What a great looking lab! Best of luck to Mackenzie Rysted at the University of Indiana...

Congrats!

May I also suggest contacting your disease-specific patient advocacy organization? For instance, I work in Parkinson's disease - and there are several societies with thousands of members here in Iowa. They need to understand the concrete impacts on patients suffering from Parkinson's disease.

How do we explain these results? We collaborated Rodica Curtu in math who implemented classic drift diffusion models. These DDMs suggest that D1 and D2 neurons provide temporal evidence. Disrupting them decreases the accumulation of temporal evidence – and predicts slowed timing.

5/5

We’ve previously reported that striatal neuron encode time by linear changes over a temporal interval – and we found that these linear changes in the striatum. However – to our complete surprise – D1 and D2 neurons had *opposite patterns* of ramping!

4/5

In line with our pharmacology data, we found that optogenetically inactivating either D2 or D1 MSNs slowed temporal control of action:
3/5

This works starts pharmacology showing that dopamine controls the timing of movement. Our work with blocking dopamine receptors systemically – and where they are most abundantly expressed – in the striatum -shows that blocking either D1 or D2 dopamine receptors slows temporal control of action:

Our latest work is up as a version of record on eLife.

elifesciences.org/articles/96287

This story a long road – but is a major advance on understanding temporal control of action.

As always, data and code are available at narayanan.lab.uiowa.edu/data
1/5

Long story short - we get great expression, and about what we might get from Cre mice. This will be a powerful tool for studying these circuits.

They will be up at Jackson (039507) soon.

Youngcho integrated FlpO - another conditional expression construct - into the D1 gene. This is distinct from the D1 Cre mice, which uses BAC transgenics:

a little girl with blue hair is looking up at the sky ALT: a little girl with blue hair is looking up at the sky

Our lab is interested in the D1 dopamine receptor. We have been using D1 Cre mice for years to identify and manipulate D1+ neurons. But what about subclasses of these neurons? What about studying them alongside other populations - such as D2 MSNs?

Generation and validation of a D1 dopamine receptor Flpo knock-in mouse - PubMed We demonstrated brain-wide GFP expression driven by Drd1-Flpo, suggesting that this mouse line may be useful for comprehensive anatomical and functional studies in many brain regions. The Drd1-Flpo mo...

Very happy that our paper describing a new D1 FLP mouse is up: pubmed.ncbi.nlm.nih.gov/39701542/

Youngcho Kim's first paper as corresponding author!

Some brief backstory (1/5)

Very proud what our nascent Center for Neurodegeneration has done here in Iowa:

Prefrontal projections to the bed nuclei of the stria terminalis modulate the specificity of aversive memories - PubMed Generalizing aversive memories helps organisms avoid danger, whereas discriminating between dissimilar situations promotes opportunistic behaviors. We identified a novel pathway that controls the cont...

All this pressure from all these new followers!

Luckily, we have a new preprint:
pubmed.ncbi.nlm.nih.gov/39569181/

Wild - the term 'prefrontal' I think first appeared in 1878 in the journal Brain relating Phineas Gage and other lesions. For the human chauvinists out there - I think the term originates from fish skull anatomy, and in the first description - animal references abound:

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