Noradrenergic Modulation of (Mal)Adaptive Behavior

Noradrenergic neuromodulation is widespread and influences behavioral states that span from sleep and wakefulness to learning and emotion regulation. Due to its vast brain-wide projection network, the locus coeruleus (LC), the brain’s chief supplier of noradrenaline, is central to these processes. Recent technological advances, including cell type- and projection-specific interrogation of neural substrates have enabled the dissection of LC function at an unprecedented level of detail. It is becoming increasingly clear that environmental stimuli engage the LC differentially, resulting in selective gating and fine-tuning of experience-dependent plasticity at varying time-scales. Furthermore, the net effect of LC engagement depends on the physiological and molecular properties of downstream circuits receiving noradrenergic innervation. Due to these complex and interdependent factors, the exact mechanisms by which NAergic neuromodulation sculpts behavioral states across an adaptive and maladaptive continuum are not fully understood.


Past research has provided some information about the afferent circuitry, cell types and downstream receptors that drive the LC’s heterogenous neuromodulatory effect on behavior. However, the precise conditions and mechanisms by which differential engagement of the noradrenergic system can tune neuronal network function underlying cognitive processes such as decision-making, emotion, and memory remain largely unresolved. Of particular interest is how modular LC function is altered in face of adversity, and how this weighs in the emergence and persistence of maladaptive memories that in turn, can promote maladaptive behaviors, including stress vulnerability. To address this gap in knowledge, a new era in noradrenergic research calls for the utilization of recent specialized technical toolkits to label, image, isolate and causally probe neuronal-network dynamics. This will enable multi-level dissection of how noradrenaline can selectively modify experience-dependent plasticity in a circuit-specific manner, promoting behavioral control of adaptive and maladaptive states.


The aim and scope of the current Research Topic is to cover promising and original discoveries that further our understanding of noradrenergic modulation of behavior, and in particular, its role in the propagation of maladaptive behavioral patterns. We encourage the submission of both clinical and preclinical research articles and urge for the dissemination of ideas originating from diverse methodologies and experimental approaches across multiple levels of analysis. Reproducibility attempts, including negative data, are especially welcomed, as the field is in need of comparative studies that might challenge the status quo. Areas to be covered in this Research Topic may include, but are not limited to:

• Cellular and molecular probing of the NAergic system in (mal)adaptive behaviors.

• Effects of pharmacological, opto- and pharmaco-genetic manipulation of the NAergic system in emotional regulation, learning & memory.

• NA role in stress-associated pathological states, such as PTSD and depression.

• Novel behavioral paradigms assessing the role of dysfunctional NA signaling in disease models.

• Secondary neurotransmitter/ neuropeptide systems that work in conjuction with or opposed to NA, to modulate behavior.


The Topic Editor Prof. dr. Merel Kindt is a founding partner of the Kindt Clinics. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: Stress, Cognition, Neuromodulation, Noradrenaline, Emotion

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.