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When danger is near food: thalamic CRF cells contribute to choice

Nature communications · 2021-05-04

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Nature communications · Research frontiers

When danger is near food: thalamic CRF cells contribute to choice

In rats, aPVT CRF-associated cells participate in conflict between food and predator cues. Accumbens output and hypothalamic input affect food seeking and defense differently.

Original Figure 6l single merged-field detail: colabeled aPVT-associated cells

Food is within reach, but a threatening odor is nearby. How does a hungry animal choose? A rat study published in Nature Communications on May 4, 2021 examines anterior paraventricular thalamus, aPVT. CRF-associated cells respond differently when food and predator cues coincide, and reducing their activity increases approach toward food. Accumbens outputs and hypothalamic inputs reveal that food-seeking suppression and defense are not uniformly controlled by the same component.

KEY FINDING

aPVT CRF-associated cells and accumbens output suppress seeking and promote avoidance. Reducing VMH–aPVT projection-associated activity weakens defense during conflict without significantly lifting food-seeking suppression.

Contents · 8 sections

Food cues remain, but seeking declines

With food cues alone, rats approach the food area and respond for reward. Predator odor adds freezing, avoidance and risk-assessment postures, while food-area time and lever pressing decline and responding begins later.

The odor changes the potential cost of approaching rather than the food itself. Greater hunger reduces some defensive responses without similarly lifting seeking suppression, separating effects of bodily need and threat cues.

Initial behavioral comparisons included both sexes, with increased defense and reduced seeking in each, while females pressed less. This provides context for individual differences within the model.

Original figure 1Food cues remain, but seeking declines
Food cues remain, but seeking declines
Figure 1: concurrent predator and food cues increase defense and reduce food approach and responding, alongside activity-label changes in several regions.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

Conflict recruits heterogeneous cellular responses

aPVT encounters food and threat information. General recordings show that cells responsive to food cues can lose those responses during conflict, while others become responsive, reorganizing the population pattern.

Within identified CRF-associated cells, the proportion responding to food cues increases during conflict, including both firing increases and decreases. The marker narrows the population without making its response uniform.

Original figure 4Conflict recruits heterogeneous cellular responses
Conflict recruits heterogeneous cellular responses
Figure 4: CRF-associated cells respond more often to food cues during conflict, with both increased and decreased firing.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

Reducing CRF population activity shifts behavior toward food

Reducing aPVT CRF-associated activity during conflict reduces avoidance, increases food approach and responding and speeds response initiation. Freezing and risk-assessment comparisons are not significant, so defense does not disappear uniformly.

Controls with isolated threat or food cues do not show the same significant effects. Conversely, activation without predator odor reduces seeking and induces place avoidance without significantly increasing overall movement or freezing.

Original figure 5Reducing CRF population activity shifts behavior toward food
Reducing CRF population activity shifts behavior toward food
Figure 5: inhibition changes avoidance and seeking during conflict without significant freezing or risk-assessment effects; activation suppresses seeking and promotes place avoidance.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

Multiple inputs and outputs converge on the thalamic node

Anatomical tracing identifies multiple aPVT CRF-associated outputs, particularly dense fibers in accumbens shell, NAcSh. Prefrontal, hypothalamic and periaqueductal inputs connect food-seeking and defensive networks.

This distribution guides functional testing without defining one closed route. CRF is a cellular identity marker here; the study does not isolate the peptide’s contribution to every behavioral effect.

Original figure 6Multiple inputs and outputs converge on the thalamic node
Multiple inputs and outputs converge on the thalamic node
Figure 6: aPVT CRF-associated cells have multiple inputs and outputs, including dense NAcSh projections.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

Accumbens output enhancement suppresses seeking and promotes avoidance

Enhancing aPVT CRF-associated terminals in NAc reduces food responding, delays response initiation and promotes avoidance of the activation-associated compartment, even without predator odor.

Total distance, maximum speed and freezing comparisons are not significant. Reduced activity within one compartment is therefore distinct from a general locomotor reduction, leaving the relevant downstream recipients to be identified.

Original figure 7Accumbens output enhancement suppresses seeking and promotes avoidance
Accumbens output enhancement suppresses seeking and promotes avoidance
Figure 7: NAc-associated terminal activation suppresses seeking and induces avoidance without significant total-distance, maximum-speed or freezing effects.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

One input has different dynamics across recipients

Both medium spiny neurons, MSNs, and cholinergic interneurons, CINs, receive excitatory input. Most paired recordings show larger MSN currents, while successive inputs facilitate CIN responses more strongly, revealing different short-term dynamics.

Downstream effects may depend on input timing as well as initial current size. Whether CINs are a decisive behavioral relay is not directly established here.

Original figure 8One input has different dynamics across recipients
One input has different dynamics across recipients
Figure 8: two NAc recipient classes show excitatory responses with different amplitudes and short-term dynamics.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

Reducing hypothalamic input weakens defense but leaves seeking suppressed

VMH cells projecting to aPVT show increased activity labeling after threat cues. Their input excites NAc-projecting aPVT cells, although the recipient recording does not independently restrict every cell to the CRF population.

Reducing VMH–aPVT projection-associated activity decreases freezing, avoidance and risk assessment during conflict, without significant changes in food approach, pressing or response latency. Isolated-threat controls lack the same effect. Less defense does not ensure renewed food seeking.

Original figure 9Reducing hypothalamic input weakens defense but leaves seeking suppressed
Reducing hypothalamic input weakens defense but leaves seeking suppressed
Figure 9: reducing VMH-associated activity decreases conflict defense without significant changes in three seeking measures; input recordings show excitatory connectivity.
Source: Engelke DS et al. · Nature communications · CC BY
Original figure and English caption ↗

Stopping and avoiding are not identical commands

The rat findings divide food–threat conflict by cell identity, output and behavior. aPVT CRF-associated activity influences seeking suppression, whereas VMH-associated input more clearly affects conflict defense. Their roles are connected but not interchangeable.

Projection-defined cells can retain collaterals, and other inputs may maintain seeking suppression. The full cell-specific relay and natural activity patterns remain unresolved. The findings distinguish stopping approach from organizing defense within a connected network.

Publication details

Engelke DS, Zhang XO, O'Malley JJ, Fernandez-Leon JA, Li S, Kirouac GJ, Beierlein M, Do-Monte FH.
A hypothalamic-thalamostriatal circuit that controls approach-avoidance conflict in rats
Nature communications · 2021-05-04
DOI: 10.1038/s41467-021-22730-y