Katharina Ziegler

Learning requires adaptive changes in neuronal circuits, but how neurons encode learning content in their activity patterns to construct memories remains poorly understood. Using longitudinal multi-site recordings in freely moving male mice performing a sensory discrimination task, we discover the emergence of burst-coding neurons (BCNs) across cortical, thalamic, and extrathalamic regions. BCNs encoded task rules through the presence or absence of bursts, with their proportion increasing as learning progressed. Decoding analyses reveal that BCNs act as the principal carriers of rule information within the thalamocortical system. BCN burst rates scaled with stimulus valence, collapsed when contingencies were degraded, and inverted after repeated rule reversals, demonstrating that bursts dynamically track associative context during learning. Indeed, pharmacological and focal genetic suppression of thalamocortical bursting disrupted learning and task performance, establishing neuronal bursts as context-sensitive drivers of associative learning. These findings identify a burst-based neural code for stimulus–outcome associations in the thalamocortical system and provide causal evidence linking cellular firing dynamics to reward contingency learning.

Aggression is a sexually dimorphic behaviour. In some species, including the laboratory mouse, it is robustly expressed in males – while females are not aggressive in the non-puerperal state. However, during nursing, females exhibit maternal aggression, a dramatic yet transient shift in their social behaviour repertoire. This phenotypic change occurring in adulthood presents an opportunity to investigate whether sex-biased behavioural programs depend on mono- or di-morphic neural circuits. While maternal hormones are known to elicit nursing, their role in maternal aggression, particularly regarding target sites and cellular mechanisms, remains unclear. Here, we show that a molecularly defined subset of mouse ventral premammillary (PMv^DAT) neurons – with an established role in intermale aggression– transitions from quiescence to a hyperexcitable state during female lactation. The maternal hormones, prolactin and oxytocin, were found to excite these cells through pre- and post-synaptic electrophysiological actions. Gain- and loss-of-function experiments related to PMv^DAT neuron activity bidirectionally influence maternal aggression, while PMv^DAT neuron activation suppressed the expression of a competing social behaviour. This study identifies a sexually monomorphic neural substrate in mice capable of integrating hormonal cues, providing a likely mechanism that enables the transient access to a dormant behavioural program.

The primary somatosensory cortex (S1) is a hub for body sensation of both innocuous and noxious signals, yet its role in somatosensation versus pain is debated. Despite known contributions of S1 to sensory gain modulation, its causal involvement in subjective sensory experiences remains elusive. Here, in mouse S1, we reveal the involvement of cortical output neurons in layers 5 (L5) and 6 (L6) in the perception of innocuous and noxious somatosensory signals. We find that L6 activation can drive aversive hypersensitivity and spontaneous nocifensive behavior. Linking behavior to neuronal mechanisms, we find that L6 enhances thalamic somatosensory responses, and in parallel, strongly suppresses L5 neurons. Directly suppressing L5 reproduced the pronociceptive phenotype induced by L6 activation, suggesting an anti-nociceptive function for L5 output. Indeed, L5 activation reduced sensory sensitivity and reversed inflammatory allodynia. Together, these findings reveal a layer-specific and bidirectional role for S1 in modulating subjective sensory experiences.

Aggression, a sexually dimorphic behaviour, is prevalent in males and typically absent in virgin females. Following parturition, however, the transient expression of aggression in adult female mice protects pups from predators and infanticide by male conspecifics. While maternal hormones are known to elicit nursing, their potential role in maternal aggression remains elusive. Here, we show in mice that a molecularly defined subset of ventral premammillary (PMv ^DAT ) neurons, instrumental for intermale aggression, switch from quiescence to a hyperexcitable state during lactation. We identify that the maternal hormones prolactin and oxytocin excite these cells through actions that include T-type Ca ²⁺ channels. Optogenetic manipulation or genetic ablation of PMv ^DAT neurons profoundly affects maternal aggression, while activation of these neurons impairs the expression of non-aggression-related maternal behaviours. This work identifies a monomorphic neural substrate that can incorporate hormonal cues to enable the transient expression of a dormant behavioural program in lactating females.