Paper We're Discussing This Week:

Kim R., Ananth M.R., Desai N.S., Role L.W., Talmage D.A. (2024) Distinct subpopulations of ventral pallidal cholinergic projection neurons encode valence of olfactory stimuli. Cell Reports 43: 114009

https://www.cell.com/cell-reports/pdf/S2211-1247(24)00337-1.pdf#page18

Previously:

Gu X., Johansen J.P. (2024) Prefrontal encoding of an internal model for emotional inference. BioRxiv: https://doi.org/10.1101/2024.04.22.590529

Li HQ, Jiang W, Ling L, Pratelli M, Chen C, Gupta V, Godavarthi SK, Spitzer NC. (2024) Generalized fear after acute stress is caused by change in neuronal cotransmitter identity. Science. 383:1252-1259. doi: 10.1126/science.adj5996.

Zhang X, Liu Y, Hong X, Li X, Meshul CK, Moore C, Yang Y, Han Y, Li WG, Qi X, Lou H, Duan S, Xu TL, Tong X. (2021) NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety. Nat Commun. 12(1):5740. doi: 10.1038/s41467-021-25956-y.

Zhu F, Elnozahy S, Lawlor J, Kuchibhotla KV. The cholinergic basal forebrain provides a parallel channel for state-dependent sensory signaling to auditory cortex. (2023) Nat Neurosci. 26:810-819. doi: 10.1038/s41593-023-01289-5.

Yamada J, Maeda S, Tojo M, Hayashida M, Iinuma KM, Jinno S. (2023) Altered regulation of oligodendrocytes associated with parvalbumin neurons in the ventral hippocampus underlies fear generalization in male mice. Neuropsychopharm. 48:1668-1679. doi: 10.1038/s41386-023-01611-6.

Sun W, Liu Z, Jiang X, Chen MB, Dong H, Liu J, Südhof TC, Quake SR. (2024) Spatial transcriptomics reveal neuron-astrocyte synergy in long-term memory. Nature. Mar;627(8003):374-381. https://www.nature.com/articles/s41586-023-07011-6

Walker EY, Pohl S, Denison RN, Barack DL, Lee J, Block N, Ma WJ, Meyniel F. (2023) Studying the neural representations of uncertainty. Nature Neuroscience, 10.1038/s41593-023-01444-y

Asokan M.M., Watanabe Y., Kimchi E.Y., Polley D.B. (2023) Potentiation of cholinergic and corticofugal inputs to the lateral amygdala in threat learning. Cell Reports 42: 113167.

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Shine JM, Müller EJ, Munn B, Cabral J, Moran RJ, Breakspear M. (2021)
Computational models link cellular mechanisms of neuromodulation to large-scale neural dynamics. Nat Neurosci. doi: 10.1038/s41593-021-00824-6.

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Companion discussion paper:

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Danielle and Margo are presenting posters on April 5 & 6 this week at the Undergraduate Research Conference.

A competitive inhibitory circuit for selection of active and passive fear responses.

Fadok JP, Krabbe S, Markovic M, Courtin J, Xu C, Massi L, Botta P, Bylund K, Müller C, Kovacevic A, Tovote P, Lüthi A.(2017) Nature, 542: 196.

An inhibitory pull-push circuit in frontal cortex.

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An intra-amygdala circuit specifically regulates social fear learning

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Distinct hippocampal pathways mediate dissociable roles of context and memory retrieval.

Xu C., Krabbe S., Grundemann J., Botta P., Fadok J., Osakada F., Saur D., Grewe B.F., Schnitzer M.J., Callaway E.M., Luthi A.

Basal forebrain neuronal inhibition enables rapid behavioral stopping

Jeffrey D. Mayse, Geoffrey M. Nelson, Irene Avila, Michela Gallagher, and Shih-Chieh Lin,

Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

Hultman R, Mague SD, Li Q, Katz BM, Michel N, Lin L, Wang J, David LK, Blount C, Chandy R, Carlson D, Ulrich K, Carin L, Dunson D, Kumar S, Deisseroth K, Moore SD, Dzirasa K.

Cortical cholinergic signaling controls the detection of cues

Howard J. Grittona , William M. Howea , Caitlin S. Mallorya , Vaughn L. Hetricka , Joshua D. Berkea , and Martin Sartera,1

A shared neural ensemble links distinct contextual memories encoded close in time

Denise J. Cai1 *, Daniel Aharoni1,2,3*, Tristan Shuman2,3*, Justin Shobe1 *, Jeremy Biane4,5, Weilin Song1 , Brandon Wei1 , Michael Veshkini1 , Mimi La-Vu1 , Jerry Lou2,3, Sergio E. Flores2,3, Isaac Kim1 , Yoshitake Sano1 , Miou Zhou1 , Karsten Baumgaertel6, Ayal Lavi1 , Masakazu Kamata7 , Mark Tuszynski4,5, Mark Mayford6, Peyman Golshani2,3 & Alcino J. Silva1

SFN 2024 in Chicago 10/5 - 10/9

October 04, 2024

Members of the lab are showing some fantastic work in Chicago this year

A season for congratulations and events!

May 24, 2024

Congratulations to Yuval who is leaving after more than 3 years in the lab to start an MD-PhD program at NYU!!

Congratulations to Nawshin who is graduating as a Valedictorian from Macaulay Honors!!

Congratulations to Mia who ran her first half-marathon, covering 13.1 miles of Brooklyn!!

Undergraduates Rock Spring Conferences - Congratulations Nawshin!

May 03, 2024

The undergrads have been doing a stellar job showcasing their work at spring conferences this year. Nawshin took home several awards for her work on the differential effects of acute vs chronic demyelination on behavior, myelin content and neural activity across the brain. Congratulations Nawshin!

Nawshin won a Best Poster award at Hunter’s UGRC.

Nawshin also won the Livingston Welch Award for Research from the Hunter Psychology Dept.

At the Hunter UGRC, George showed how chronic stress results in increased anxiety-like behavior even during a prolonged exposure to a non-stressful environment.

Congratulations to Dr. Carolina M. Fernandes-Henriques!!

March 14, 2024

On January 16th, Carolina beautifully defended her thesis, “The Role of the Infralimbic-Basal Forebrain Pathway in Fear Extinction”. It was a wonderful event and the first manuscript from her work is on its way out.

A heartfelt thank you to Carolina’s fantastic committee: Rob Froemke, Allyson Friedman, Andy Delamater, and Susana Mingote. Their contributions and discussions were most welcome and appreciated.

As Carolina is getting a PhD, she showed us her matrilineal lineage in Portugal. Each succeeding generation achieves a more advanced degree.

Lots of love came in from the room and via Zoom from Portugal.

Dr. Henriques’s celebratory cake and cheese bounty

Congratulations to Rhonda and Emma!

December 06, 2023

Congratulations to Rhonda (seen here as Green Fluorescent Protein) on passing her qualifying exam and moving on to candidacy!

Congratulations to Emma (seen here as Dylight 405) for getting accepted to the Advanced Neuroimaging Techniques course at Max Planck and for winning a Travel Award!

The Fluorescent Proteins at the Biology Halloween party

SFN 2023

December 06, 2023

We had a great time catching up with all the people, the science, and the tech at SfN in DC.

Breakfast Club style at SfN in DC (missing Nawshin, George, and Katie)

Carolina showing her thesis work on circuit communication during extinction learning

Emma showing her thesis work on oligodendrocyte - neuron interactions in learning

The mysteries of the Olive Garden were sampled en route back to NYC

Catch up with us at SFN

November 11, 2023

We will be at SFN, presenting our work and that of others.

Webinar on Making Posters for SFN

November 01, 2023

If you’re new to making posters, take a look at our SFN Webinar on “How To Make and Present a Poster”. In it, Marina Picciotto, Steve Maren, and I discuss various aspects of making a poster (from visuals to content), how to present to different audiences, and how to organize post-presentation networking.

https://neuronline.sfn.org/professional-development/how-to-make-and-present-a-poster-for-neuroscience-2023

Also, take a look at the webinar “Maximizing Your Time at SFN’s Annual Meeting” with Janice Naegele and Veronica Galvin, for strategies on how to prevent feeling overwhelmed.

Why am I scared of bridges?

October 06, 2023

BBC Crowd Science (produced by Hannah Fisher, hosted by Caroline Steel) covered phobias in an episode titled “Why am I scared of bridges?”, where we discussed the circuitry of fear, and Caroline covers lots of other aspects of phobias, such as cultural influences and therapeutic approaches. Caroline even gets therapy for her phobia of elevators. Take a listen.

Pavlovian 2023 in Austin TX

September 28, 2023

We had a wonderful time presenting our work and learning from others at the Pavlovian conference in Austin. Lots of interesting talks, posters, and people.

Carolina and Emma showing their projects

Emma’s confocal images of PV cells are great for staging a talk that showcases the role of prefrontal interneurons

Jinah and Mia went full TX with the bolo ties

IBRO 2023

September 14, 2023

The IBRO conference in Granada was lots of fun with 5 days of great science in a beautiful city. Sara Mederos (Wellcome Center, UCL) and Mario Martin-Fernandez (University of Bordeaux) organized a wonderful symposium, “From Negative Emotion to Defensive Behaviors”, where Sara, Mario, Rony Paz (Weizmann Institute), and I shared new data on circuits of emotion regulation. Olé!

Lab life catch up!

August 11, 2023

A lot has happened - it’s time to turn on the time machine and catch up a little bit.

Our summer student Ariana did a wonderful job presenting her summer project at the NYU GSTEM event to wrap up her 5 weeks with us in the lab. Special thanks to George and Katie for teaching Ariana about behavioral analysis and cell sorting, and to Mia for showing her all sorts of lab techniques!

Carolina won the Best Scientific Presentation Award at the CUNY Sci Comm event held at the Advanced Science Research Center.

Society of Biological Psychiatry - Symposium on The Role of Somatostatin Interneurons in Affective and Cognitive Disorders with Nikki Crowley (Penn State), Thomas Prevot (University of Toronto), and Dave Kupferschmidt (NIMH)

Yuval presented her work at the Eastern Psychological Association in Boston and at the Hunter UGRC, and Nawshin showed her work at the CUNY wide STEM conference and at the Hunter UGRC

Secret Lab Mate Dinner of 2022 was actually celebrated in 2023!

How could we not attend the “Life of a Neuron” exhibit at Artechouse?

SFN 2022 in San Diego was little photographed, but much enjoyed

CUNY Neuro Seminar Fri 2/10: Alain Frigon

February 10, 2023

“Inhibition and facilitation of spinal circuits by sensory inputs from the lumbar and perineal regions after spinal cord injury”

Dr. Alain Frigon (Université de Sherbrooke, Canada)

Email: el1417 at hunter dot cuny dot edu for link to join seminar

CUNY Neuro Seminar: Orie Shafer - Jan 27 @3pm EST!

January 27, 2023

Kicking off our Spring 2023 Seminar Series is our own Orie Shafer!

Dr. Orie Shafer (ASRC, CUNY)

Circadian and Homeostatic Regulation of Sleep in an Insect Brain

Sleep is the foundation of health and well-being and is regulated by two major processes residing within the animal brain: circadian timekeeping and homeostatic sleep control. These processes are highly conserved and genetically tractable invertebrate model systems have consistently enriched and informed our understanding their operation in mammalian brains. In this seminar, I will briefly summarize ~20 years of my lab's work on the circadian clock in Drosophila brain and highlight new work focused on how circadian timekeeping and sleep homeostasis cooperate to control sleep timing and duration in the fly.

To join, email: el1417 at hunter dot cuny dot edu

Dec 5 Biology Seminar: Dr. Leora Yetnikoff

December 04, 2022

Monday, December 5th at 12:30pm EST

“Axo-glial interactions between midbrain dopamine axons and oligodendrocyte lineage cells and their implications for experience-dependent myelination.”

Dr. Leora Yetnikoff (CSI, CUNY)

email el1417 at hunter dot cuny dot edu for a link to join

Our new myelin work made a Pavlovian debut

October 03, 2022

What a terrific conference! We very much enjoyed catching up with all the interesting new projects and directions in the field of learning, Emma showed our new work looking at experience-dependent myelin remodeling in the prefrontal cortex, we ran a lively symposium on the Generalization of Learning, attended breakout sessions and enjoyed the Women In Science luncheon to boot. Looking forward to next year in Austin!

The Pavlovian Conference is coming!

September 28, 2022

Nesha Burghardt and I will be chairing a symposium on The Generalization of Learning this coming Saturday at the Pavlovian conference in Milwaukee. We are looking forward to all the interesting ways the speakers think about generalization in their work:

Jelena Radulovic: “Retrieval-based generalization of aversive conditioning”

Larry Zweifel: “The role of dopamine in threat generalization”

Maria Geffen: “A cortico-thalamic circuit for learning generalization”

Joey Dunsmoor: “Latent associative structures facilitate higher-order transfer of learned fear”

The conference is packed with wonderful talks and symposia on the interactions between stress and learning, social and appetitive learning, habit formation, safety learning, effects of drugs and alcohol on learning and memory, learning about context, and on!

Summer 2022 is over?

September 14, 2022

The summer flew by with lots of activity and little posting about it. One highlight was going to FENS, where Carolina showed our work on the medial prefrontal cortex-basal forebrain circuit in extinction. It was a great meeting, seeing colleagues in person was a treat, and Paris is still beautiful!

Looks like there are some well-clustered single units around the Eiffel Tower.

New Paper Out!

May 06, 2022

Our new paper, Prelimbic cortex drives discrimination of non-aversion via amygdala somatostatin interneurons is now out online at Neuron. This paper grew out of our interest in the mechanisms the brain uses to discriminate non-threatening stimuli, and suppress fear. Our findings are summarized in this graphic, with a deeper dive into the data below.

Inputs from the medial prefrontal cortex (mPFC) to the amygdala drive activation of inhibitory somatostatin-expressing interneurons (SOM). This desynchronizes amygdala pyramidal cells, decreasing defensive freezing and generalized fear (left). When the mPFC input is absent, this mechanism fails, and more generalized fear is observed.

We first show that when non-threatening stimuli are remembered and fear is suppressed, the inhibitory somatostatin-expressing (SOM) interneurons of the basolateral amygdala become active.

2-photon recordings of somatostatin (SOM) -expressing interneurons in the basolateral amygdala show increased activation to the non-threatening CS- (shown in blue) relative to the threatening CS+ (shown in red).

When just the non-threatening CS- is remembered, there is more activity in SOM interneurons than in parvalbumin-expressing (PV) interneurons of the amygdala.

Interestingly, when we inhibited amygdala SOM interneurons, this resulted in increased fear generalization. The potential cellular mechanism of this behavioral finding is intriguing because SOM interneurons target dendrites of amygdala pyramidal cells, and could act to filter out incoming input, preventing the pyramidal cells from synchronous activation. And indeed, our recordings show that during a non-threatening cue, amygdala activity is less synchronous, but when SOM interneurons are inhibited, it becomes more synchronized in the theta-band response.

During the non-threatening CS-, amygdala activity shows less theta reset than during the aversive CS+ (left). However, when SOM interneurons are inhibited, CS- theta reset increases, indicating more synchronous activation of amygdala cell firing (right).

When SOM interneurons are inhibited in the amygdala during the non-threatening CS- (light blue line), the firing rate of pyramidal cells becomes more modulated by the theta-frequency.

Given that the prelimbic cortex is important for fear discrimination learning, we inhibited it, to see if it affects SOM activity and synchrony in the amygdala, as well as behavior. We found that inhibiting the prelimbic cortex increased generalized fear, decreased SOM interneuron activity in the amygdala, and resulted in increased cue-evoked theta synchrony. We also find, that stimulating prelimbic inputs to the amygdala during memory retrieval, improved discrimination in animals that otherwise showed generalized fear.