Neurotensin orchestrates valence assignment in the amygdala

Li, Hao; Namburi, Praneeth; Jm, Olson; Borio, Matilde; Lemieux, Mackenzie; Beyeler, Anna; Calhoon, Gwendolyn G.; HitoraーImamura, Natsuko; Coley, Austin A.; Libster, Avraham; Bal, Aneesh; Jin, Xin; Wang, Huan; Jia, Caroline; Choudhury, Sourav; Shi, Xi; Felix-Ortiz, Ada C.; Fuente, Verónica de la; Barth, Vanessa P; King, Hunter Oren; Izadmehr, Ehsan M.; Revanna, Jasmin S.; Batra, Kanha; Fischer, Kathleen M.; Keyes, Laurel; Padilla-Coreano, Nancy; Siciliano, Cody A.; McCullough, Kenneth M.; Wichmann, Romy; Ressler, Kerry J.; Fiete, Ila; Zhang, Feng; Li, Yulong; Tye, Kay M.

doi:10.1038/s41586-022-04964-y

Cited by 60 publications

(48 citation statements)

References 56 publications

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“…The brain devotes an essential thalamic mechanism for distinguishing the direction of emotional signals, relying on the production and release of neurotensin for rewards, but punishment learning comes for free [ 101 ]. Publications by reputable laboratories support our working hypothesis on the contrasting metabolisms positive and negative emotions.…”

Section: Discussionmentioning

confidence: 99%

“…Rapid switching of a high-dimensional resting state shrinks the variance as activations collapse into lower-dimensional attractor dynamics [ 10 , 98 , 99 ] based on whether experiences represent positive or negative charge [ 100 ]. The brain devotes an essential thalamic mechanism for distinguishing the direction of emotional signals, relying on the production and release of neurotensin for rewards, but punishment learning comes for free [ 101 ]. The above results strongly suggest that positive and negative emotions have contrasting energy metabolisms, and correlate to endothermic or exothermic cycles, respectively.…”

Section: Thermodynamic Regulation Of the Neural Systemmentioning

confidence: 99%

“…Thus, information storage is an energy requiring process [ 115 ], analogous to a “phase transition” due to a temperature decrease in a physical system [ 22 ]. We have shown that positive memory formation requires energy [ 115 , 119 ] arising from the polar emotional experience processing [ 101 ]. Thus, the system can acquire new information in the following cycle while leaving the stored information accessible for decision-making.…”

Section: Thermodynamic Regulation Of the Neural Systemmentioning

confidence: 99%

“…In summary, neurotensin production, synaptic reorganization and neurogenesis contribute to the endothermic cycle’s energy need [ 101 , 115 ]. The endothermic cycle confirms the physical relationship between intelligence and entropy maximization [ 54 ].…”

Section: Thermodynamic Regulation Of the Neural Systemmentioning

confidence: 99%

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How the Brain Becomes the Mind: Can Thermodynamics Explain the Emergence and Nature of Emotions?

Deli

Peters

Kisvárday

2022

Entropy

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The neural systems’ electric activities are fundamental for the phenomenology of consciousness. Sensory perception triggers an information/energy exchange with the environment, but the brain’s recurrent activations maintain a resting state with constant parameters. Therefore, perception forms a closed thermodynamic cycle. In physics, the Carnot engine is an ideal thermodynamic cycle that converts heat from a hot reservoir into work, or inversely, requires work to transfer heat from a low- to a high-temperature reservoir (the reversed Carnot cycle). We analyze the high entropy brain by the endothermic reversed Carnot cycle. Its irreversible activations provide temporal directionality for future orientation. A flexible transfer between neural states inspires openness and creativity. In contrast, the low entropy resting state parallels reversible activations, which impose past focus via repetitive thinking, remorse, and regret. The exothermic Carnot cycle degrades mental energy. Therefore, the brain’s energy/information balance formulates motivation, sensed as position or negative emotions. Our work provides an analytical perspective of positive and negative emotions and spontaneous behavior from the free energy principle. Furthermore, electrical activities, thoughts, and beliefs lend themselves to a temporal organization, an orthogonal condition to physical systems. Here, we suggest that an experimental validation of the thermodynamic origin of emotions might inspire better treatment options for mental diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Thermodynamic Regulation Of the Neural Systemmentioning

confidence: 99%

Section: Thermodynamic Regulation Of the Neural Systemmentioning

confidence: 99%

Section: Thermodynamic Regulation Of the Neural Systemmentioning

confidence: 99%

See 2 more Smart Citations

How the Brain Becomes the Mind: Can Thermodynamics Explain the Emergence and Nature of Emotions?

Deli

Peters

Kisvárday

2022

Entropy

View full text Add to dashboard Cite

show abstract

“…However, an unresolved mystery in current models of amygdala function is the discrepancy in timescales between the activity of amygdala complex neurons and the conditioned behaviors that they drive. Neurons in the amygdala exhibit increased responses to a conditioned stimulus (CS), but these are often only transient, lasting less than a second from the onset of a sensory stimulus (Goosens and Maren, 2004;Li et al, 2022;Quirk et al, 1995Quirk et al, , 1995Tye et al, 2008;Whittle et al, 2021). This does not match the behaviors that can be elicited by these stimuli, which include defensive responses expressed for the full duration of the threat presentation that would be essential to survive or evade threats in the real world.…”

Section: Introductionmentioning

confidence: 99%

Amygdalostriatal transition zone neurons encode sustained valence to direct conditioned behaviors

Mills

Lee

Howe

et al. 2022

Preprint

Self Cite

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In order to respond appropriately to threats in the environment, the brain must rapidly determine whether a stimulus is important and whether it is positive or negative, and then use that information to direct behavioral responses. Neurons in the amygdala have long been implicated in valence encoding and in fear responses to threatening stimuli, but show transient firing responses in response to these stimuli that do not match the timescales of associated behavioral responses. For decades, there has been a logical gap in how behavioral responses could be mediated without an ensemble representation of the internal state of valence that has rapid onset, high signal-to-noise, and is sustained for the duration of the behavioral state. Here, we present the amygdalostriatal transition zone (ASt) as a missing piece of this highly conserved process that is of paramount importance for survival, which does exactly this: represents an internal state (e.g. fear) that can be expressed in multiple motor outputs (e.g. freezing or escape). The ASt is anatomically positioned as a 'shortcut' to connect the corticolimbic system (important for evaluation) with the basal ganglia (important for action selection) with the inputs of the amygdala and the outputs of the striatum - ideally poised for evaluating and responding to environmental threats. From in vivo cellular resolution recordings that include both electrophysiology and calcium imaging, we find that ASt neurons are unique in that they are sparse coding, extremely high signal-to-noise, and also maintain a sustained response for negative valence stimuli for the duration of the defensive behavior - a rare but essential combination. We further show that photostimulation of the ASt is sufficient to drive freezing and avoidance behaviors. Using single-nucleus RNA sequencing and in situ RNA labelling we generate a comprehensive profile of cell types and gene expression in the ASt, and find the ASt is genetically distinct from adjacent striatal and amygdalar structures. We also find that the ASt has a greater proportion of neurons expressing Drd2 than neurons expressing Drd1a, a unique feature compared to other regions of the striatum. Using in vivo calcium imaging, we show that that this Drd2+ population robustly encodes stimuli of negative valence, and in loss-of-function experiments find that optogenetic inhibition of Drd2+ ASt neurons causes a striking reduction in cue-conditioned fear responses. Together, our findings identify the ASt as a previously-unappreciated critical missing link for encoding learned associations and directing ongoing behavior.

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Spatial transcriptomic analysis of the mouse brain following chronic social defeat stress

Wang,

Song,

Zhao

et al. 2023

Exploration

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Depression is a highly prevalent and disabling mental disorder, involving numerous genetic changes that are associated with abnormal functions in multiple regions of the brain. However, there is little transcriptomic‐wide characterization of chronic social defeat stress (CSDS) to comprehensively compare the transcriptional changes in multiple brain regions. Spatial transcriptomics (ST) was used to reveal the spatial difference of gene expression in the control, resilient (RES) and susceptible (SUS) mouse brains, and annotated eight anatomical brain regions and six cell types. The gene expression profiles uncovered that CSDS leads to gene synchrony changes in different brain regions. Then it was identified that inhibitory neurons and synaptic functions in multiple regions were primarily affected by CSDS. The brain regions Hippocampus (HIP), Isocortex, and Amygdala (AMY) present more pronounced transcriptional changes in genes associated with depressive psychiatric disorders than other regions. Signalling communication between these three brain regions may play a critical role in susceptibility to CSDS. Taken together, this study provides important new insights into CSDS susceptibility at the ST level, which offers a new approach for understanding and treating depression.

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Neurotensin orchestrates valence assignment in the amygdala

Cited by 60 publications

References 56 publications

How the Brain Becomes the Mind: Can Thermodynamics Explain the Emergence and Nature of Emotions?

How the Brain Becomes the Mind: Can Thermodynamics Explain the Emergence and Nature of Emotions?

Amygdalostriatal transition zone neurons encode sustained valence to direct conditioned behaviors

Spatial transcriptomic analysis of the mouse brain following chronic social defeat stress

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