A dormant network of brain cells present in female mice awakens after they give birth, repurposing a neural circuit otherwise used by males to give mothers the ability to perform aggressive, defensive behaviors. Researchers at Stockholm University and the Karolinska Institutet found that this previously “silent” group of nerve cells becomes responsive to maternal hormones, flipping a switch that temporarily grants access to a behavioral program outside the normal female repertoire.
The discovery provides a stunning example of the brain’s plasticity, showing how a single, sexually monomorphic neural substrate—a circuit that exists in both males and females—can be functionally toggled on or off depending on the animal’s life stage. By identifying the specific cells and the hormonal triggers that control this latent system, the findings open new avenues for understanding how the brain dynamically adapts to meet the survival needs of an individual and its offspring.
A Hidden Neural Substrate
The investigation centered on a small, molecularly-defined group of cells known as PMvDAT neurons, located in the ventral premammillary nucleus of the brain. This region was already well-established for its crucial role in driving intermale aggression, the characteristic fighting behavior males use to establish social hierarchy and secure resources. In virgin female mice, who are typically not aggressive, scientists observed that these specific neurons remained quiescent and unresponsive.
This research demonstrates that the neural hardware for aggression is not exclusive to males. Instead, the same network of cells that drives aggression in males lies dormant in females. The critical difference is not the presence of the circuit, but the hormonal environment required to activate it. This finding challenges previous assumptions about sexually dimorphic behaviors depending entirely on structurally dimorphic brain circuits, suggesting a more flexible model of neural control.
The Hormonal Ignition Switch
The dramatic transformation from a peaceful virgin female to a defensive mother is orchestrated by hormones that surge during and after pregnancy. The study identified two key maternal hormones, prolactin and oxytocin, as the agents that awaken the dormant PMvDAT neurons. While these hormones are primarily known for their roles in lactation and social bonding, the research reveals they also act as a powerful ignition switch for the aggression circuit.
Researchers found that prolactin and oxytocin excite these cells through both pre- and post-synaptic electrophysiological actions. This hormonal bath effectively primes the neurons, transitioning them from a silent state to a hyperexcitable one. During lactation, when hormone levels are high, the once-unresponsive cells become highly sensitive and ready to fire, enabling the mother to react aggressively to threats against her pups.
Advanced Methods Confirm Causality
To definitively prove that the PMvDAT neurons were directly responsible for maternal aggression, the team employed sophisticated genetic and optical techniques to control the cells’ activity in real time.
Optogenetic Activation
Using a technique called optogenetics, scientists introduced a light-sensitive protein (channelrhodopsin-2) into the target neurons of lactating mother mice. This allowed them to activate the cells simply by shining a light on them. The results were immediate and unambiguous: optogenetic stimulation of PMvDAT cells caused mothers to launch prolonged attack bouts against male intruders within seconds. This gain-of-function experiment confirmed that activating this specific circuit is sufficient to trigger the aggressive behavior.
Inactivation and Deletion
The team then performed the opposite experiment to see if the behavior would disappear without these neurons. When they silenced the PMvDAT neurons in the mother mice, the animals stopped attacking cage intruders, confirming that the activity of these cells is necessary for maternal aggression. Further loss-of-function experiments, in which the neurons were genetically ablated, or deleted, produced the same profound effect, cementing the causal link between this specific cell population and the defensive behavior.
State-Dependence and Behavioral Trade-Offs
Interestingly, the power of the PMvDAT circuit appears to be state-dependent, requiring the unique neurochemical environment of a maternal brain to function as an aggression switch. When researchers activated the same neurons in virgin female mice, it did not trigger aggression. Instead, the non-mothers displayed an increase in close investigation of the other mouse, suggesting the brain’s overall state dictates the behavioral output of the circuit’s activation.
Furthermore, the study revealed a behavioral trade-off associated with the system. Activating the aggression circuit in mothers actively suppressed other essential maternal behaviors. For example, a mother undergoing photostimulation of these neurons would not retrieve her pups, even in the absence of an intruder. This suggests the brain prioritizes the defensive program at the expense of other competing social behaviors like nursing or pup care when a threat is perceived.
Implications for Brain Plasticity and Behavior
This work provides a powerful new framework for understanding how complex behaviors can remain dormant until they are needed for survival. According to first author Stefanos Stagkourakis, “it turned out that the same network of cells that drive aggression in male mice lies dormant in females—until motherhood flips the switch of this hormone-sensitive system.” The findings illustrate a mechanism for how the brain can transiently mobilize a latent behavioral program.
While the researchers caution that the study was conducted on laboratory mice and it is not yet known if the results can be transferred to humans, the mechanism itself has broader significance. It highlights how a single neural circuit, present in both sexes, can be flexibly regulated by hormones to produce vastly different behavioral repertoires. This principle may apply to other contexts where individuals must gain temporary access to behaviors outside their usual set of skills to adapt and survive.