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Ventromedial hypothalamic neurons control a defensive emotion state.

Kunwar PS, Zelikowsky M, Remedios R, Cai H, Yilmaz M, Meister M, Anderson DJ - Elife (2015)

Bottom Line: The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself.Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center.These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.

View Article: PubMed Central - PubMed

Affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.

ABSTRACT
Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.

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Optogenetic stimulation of SF1+ neurons induces aversion and interrupts ongoing consummatory behaviors.(A) Representative tracking traces of ChR2 mouse (top) and eYFP control mouse (bottom) in a real-time place avoidance assay (RTPA). Photostimulation (blue bar) was delivered in a manual closed-loop manner depending on the animal's behavior (see text). (B) Percentage of total time (20 min) spent in stimulated side during 20-min trial. (C) Average latency to withdraw from the stimulated side. (D) Average velocity to enter or exit the stimulated side for the first (left) vs last trial (right). (E) Latency to withdraw from the stimulated side for the first vs last trials. n = 6–7 animals for each condition in D and E. (F) Sample video still frames taken from consummatory behavioral assays. (G) Percentage of indicated behavior episodes terminated by light stimulation during the behavior within 6 s of photostimulation onset. (H) Latency to terminate respective consummatory behavior during photostimulation. n = 4–6 mice per condition. Values are displayed as mean ± SEM. ****p < 0.001; ***p < 0.001; **p < 0.01; *p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.06633.010
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fig4: Optogenetic stimulation of SF1+ neurons induces aversion and interrupts ongoing consummatory behaviors.(A) Representative tracking traces of ChR2 mouse (top) and eYFP control mouse (bottom) in a real-time place avoidance assay (RTPA). Photostimulation (blue bar) was delivered in a manual closed-loop manner depending on the animal's behavior (see text). (B) Percentage of total time (20 min) spent in stimulated side during 20-min trial. (C) Average latency to withdraw from the stimulated side. (D) Average velocity to enter or exit the stimulated side for the first (left) vs last trial (right). (E) Latency to withdraw from the stimulated side for the first vs last trials. n = 6–7 animals for each condition in D and E. (F) Sample video still frames taken from consummatory behavioral assays. (G) Percentage of indicated behavior episodes terminated by light stimulation during the behavior within 6 s of photostimulation onset. (H) Latency to terminate respective consummatory behavior during photostimulation. n = 4–6 mice per condition. Values are displayed as mean ± SEM. ****p < 0.001; ***p < 0.001; **p < 0.01; *p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.06633.010

Mentions: The undirected nature of the defensive responses evoked by photostimulation of SF1+ neurons in the animals' home cage left open the question of whether activation of these cells can promote avoidance or withdrawal. To investigate this question, we tested whether photostimulation of SF1+ neurons was sufficient to generate real-time place aversion (RTPA) (Stamatakis and Stuber, 2012; Kim et al., 2013). Mice expressing ChR2 in SF1+ neurons were randomly placed on one side of a contextually identical two-chamber place preference box (Stamatakis and Stuber, 2012) (Figure 4A). Photostimulation was delivered using a manual closed-loop protocol: the laser was switched on by the observer as soon as the mouse spontaneously entered the side opposite the one in which he had initially been placed; stimulation was continued until the animal moved to the non-stimulated side, at which point the laser was switched off. This stimulation regime was carried out over 20 min. Light pulses were delivered at low intensity (0.01 mW/mm2), below the threshold required to elicit robust freezing or activity bursts.10.7554/eLife.06633.010Figure 4.Optogenetic stimulation of SF1+ neurons induces aversion and interrupts ongoing consummatory behaviors.


Ventromedial hypothalamic neurons control a defensive emotion state.

Kunwar PS, Zelikowsky M, Remedios R, Cai H, Yilmaz M, Meister M, Anderson DJ - Elife (2015)

Optogenetic stimulation of SF1+ neurons induces aversion and interrupts ongoing consummatory behaviors.(A) Representative tracking traces of ChR2 mouse (top) and eYFP control mouse (bottom) in a real-time place avoidance assay (RTPA). Photostimulation (blue bar) was delivered in a manual closed-loop manner depending on the animal's behavior (see text). (B) Percentage of total time (20 min) spent in stimulated side during 20-min trial. (C) Average latency to withdraw from the stimulated side. (D) Average velocity to enter or exit the stimulated side for the first (left) vs last trial (right). (E) Latency to withdraw from the stimulated side for the first vs last trials. n = 6–7 animals for each condition in D and E. (F) Sample video still frames taken from consummatory behavioral assays. (G) Percentage of indicated behavior episodes terminated by light stimulation during the behavior within 6 s of photostimulation onset. (H) Latency to terminate respective consummatory behavior during photostimulation. n = 4–6 mice per condition. Values are displayed as mean ± SEM. ****p < 0.001; ***p < 0.001; **p < 0.01; *p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.06633.010
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fig4: Optogenetic stimulation of SF1+ neurons induces aversion and interrupts ongoing consummatory behaviors.(A) Representative tracking traces of ChR2 mouse (top) and eYFP control mouse (bottom) in a real-time place avoidance assay (RTPA). Photostimulation (blue bar) was delivered in a manual closed-loop manner depending on the animal's behavior (see text). (B) Percentage of total time (20 min) spent in stimulated side during 20-min trial. (C) Average latency to withdraw from the stimulated side. (D) Average velocity to enter or exit the stimulated side for the first (left) vs last trial (right). (E) Latency to withdraw from the stimulated side for the first vs last trials. n = 6–7 animals for each condition in D and E. (F) Sample video still frames taken from consummatory behavioral assays. (G) Percentage of indicated behavior episodes terminated by light stimulation during the behavior within 6 s of photostimulation onset. (H) Latency to terminate respective consummatory behavior during photostimulation. n = 4–6 mice per condition. Values are displayed as mean ± SEM. ****p < 0.001; ***p < 0.001; **p < 0.01; *p < 0.05.DOI:http://dx.doi.org/10.7554/eLife.06633.010
Mentions: The undirected nature of the defensive responses evoked by photostimulation of SF1+ neurons in the animals' home cage left open the question of whether activation of these cells can promote avoidance or withdrawal. To investigate this question, we tested whether photostimulation of SF1+ neurons was sufficient to generate real-time place aversion (RTPA) (Stamatakis and Stuber, 2012; Kim et al., 2013). Mice expressing ChR2 in SF1+ neurons were randomly placed on one side of a contextually identical two-chamber place preference box (Stamatakis and Stuber, 2012) (Figure 4A). Photostimulation was delivered using a manual closed-loop protocol: the laser was switched on by the observer as soon as the mouse spontaneously entered the side opposite the one in which he had initially been placed; stimulation was continued until the animal moved to the non-stimulated side, at which point the laser was switched off. This stimulation regime was carried out over 20 min. Light pulses were delivered at low intensity (0.01 mW/mm2), below the threshold required to elicit robust freezing or activity bursts.10.7554/eLife.06633.010Figure 4.Optogenetic stimulation of SF1+ neurons induces aversion and interrupts ongoing consummatory behaviors.

Bottom Line: The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself.Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center.These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.

View Article: PubMed Central - PubMed

Affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.

ABSTRACT
Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.

Show MeSH
Related in: MedlinePlus