Biology subjects

Johansen, J. P.

Publications and source records attributed to Johansen, J. P..

8 recordsLinked to original sources

bioRxiv2026

A sensorimotor brain circuit for transforming aversive experiences into emotional states

Innately aversive experiences produce emotional states which control behavior as well as long term associative memories1-3. Brainstem regions engage innate defensive reactions1,3-7, but it is unclear how the nervous system transduces external aversive experiences into higher order, emotional representations in the forebrain to instruct learning and modulate behavior. The prevailing view is that the sensory properties of aversive experiences activate forebrain emotional processing1,3,8-10, but classical theories proposed that internal bodily reactions to unpleasant events produce feeling states11,12. Here we identify a brainstem cuneiform (CnF) circuit which conveys information about both the external sensory causes and internal motor reactions related to aversive events to the lateral/basal nuclei of the amygdala (LA/B), a brain region which stores emotional memories, to enhance ongoing defensive behaviors and regulate associative memory formation. Glutamatergic CnF neurons project directly to LA/B and receive afferent inputs from aversive-sensory and aversive-motor brain regions. Notably, LA/B neurons encode a sensorimotor state in response to noxious stimuli, with both sensory and motor features transmitted through the CnF-to-LA/B pathway. Finally, optogenetic perturbation experiments showed that during aversive experiences, the CnF-LA/B circuit instructs emotional memory formation and enhances the intensity of ongoing defensive behaviors. These findings reveal how the nervous system constructs an aversive sensorimotor state in the amygdala used for regulating the strength of emotional behaviors and producing memory formation. This demonstrates a clinically relevant brain mechanism for the regulation of emotional processing by both external traumatic events and the accompanying bodily reactions.

neuroscience↗

bioRxiv2025

A neural circuit targeting technique for investigating functional input-output organization in the nervous system

Neurons communicate information across circuits and the function of cells in these circuits is determined by both the afferent inputs they receive and the efferent outputs they send to other brain regions1,2. To study the activity and function of specific neuronal populations, transneuronal anterograde3 and retrograde4-6 viral approaches have been employed to define neural circuit elements by inputs or outputs, respectively. However, what is missing is a way to study the function of neurons based on both their inputs and outputs. Applying a combination of multiple recombinases and transneuronal anterograde/retrograde viruses, we developed a technique called input-output Projection-based INtersectional Circuit-tagging Enabled by Recombinases (PINCER) to target specific neuronal cell types and investigate functional input-output organization in neural circuits. We show the logic and application of this technique with in vivo calcium imaging and optogenetic approaches to reveal the distinct functions and neural dynamics of connectivity defined neuronal populations in the amygdala for emotional processing. Specifically, PINCER allowed the parsing of valence and salience functions of the amygdala to reveal an input-output cell type selectively mediating aversive memory formation. This technique allows neuroscientists to identify novel subclasses of cells based on their combinatorial input-output anatomical connectivity, providing a tool for fine dissection of the functional properties of neural circuits.

neuroscience↗

bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

neuroscience↗

bioRxiv2024

Bidirectional emotional regulation through prefrontal innervation of the locus coeruleus

Traumatic experiences produce powerful emotional memories which can subsequently be enhanced or reduced through cognitive control mechanisms. Noradrenaline from the brainstem locus coeruleus (LC) is activated during aversive emotion-inducing experiences and upregulated in individuals suffering from anxiety and trauma related disorders. The medial prefrontal cortex (mPFC) participates in cognitive and emotional control processes such as production of learned defensive responses and suppression of aversive memories through extinction. However, it is unclear whether or how distinct mPFC regions influence the LC to regulate learned emotional responding. Using viral based anatomical tracing techniques, we found that the LC receives topographically organized projections from the prelimbic (PL) and infralimbic (IL) subregions of mPFC. Furthermore, optogenetic approaches revealed that PL and IL inputs to LC are required to inhibit or facilitate, respectively, the extinction of aversive memories. Moreover, LC-projecting neurons in PL and IL exhibited distinct activity patterns during extinction learning, with IL-to-LC neurons displaying sustained, sensory cue-evoked activation, while activity in PL-to-LC inputs is elevated during periods of externally and internally generated aversive emotional responding. Together, these results demonstrate that mPFC subregions bidirectionally regulate extinction of emotional memories through differential modulation of the LC-noradrenaline system.

neuroscience↗

bioRxiv2023

Emotional association enhances perceptual memory through amygdalo-cortical inputs during NREM sleep

Emotional arousal is thought to enhance the consolidation of associated memories by activating the basolateral amygdala (BLA) and its projections to memory-storing regions1-4. Although the importance of both rapid eye movement (REM) and non-REM (NREM) sleep-state specific BLA activity for emotional memory processing has been proposed5-9, how and when the BLA interacts with other brain regions to enhance memory consolidation remains unclear10. Here, by adding emotional information to a perceptual recognition task that relies on top-down inputs from frontal to sensory cortices, we demonstrated that the BLA not only associates emotional information with perceptual information, but also enhances the retention of associated perceptual memory through BLA-frontal projections. Electrophysiological recordings revealed that emotional association increases the reactivation of coordinated activity across the BLA-frontal-sensory region during NREM sleep, but not during REM sleep. Notably, this inter-regional coordinated reactivation during NREM sleep was entrained to the BLA high-frequency oscillations in the emotional condition, suggesting that the BLA triggers inter-regional interaction. Optogenetic silencing of BLA terminals in the frontal cortex during NREM sleep, but not REM sleep, disrupted the enhanced retention of the perceptual memory, but not the association itself or the emotional component of associative memory. Our results indicate that the inter-regional coordination through the BLA-cortical inputs during NREM sleep is causally required for memory enhancement by emotional arousal.

neuroscience↗

bioRxiv2022

Whole-brain afferent input mapping to functionally distinct brainstem noradrenaline cell types

The locus coeruleus (LC) is a small region in the pons and the main source of noradrenaline (NA) to the forebrain. While traditional models suggested that all LC-NA neurons project indiscriminately throughout the brain, accumulating evidence indicates that these cells can be heterogeneous based on their anatomical connectivity and behavioral functionality and exhibit distinct coding modes. How LC-NA neuronal subpopulations are endowed with unique functional properties is unclear. Here, we used a viral-genetic approach for mapping anatomical connectivity at different levels of organization based on inputs and outputs of defined cell classes. Specifically, we studied the whole-brain afferent inputs onto two functionally distinct LC-NA neuronal subpopulations which project to amygdala or medial prefrontal cortex (mPFC). We found that the global input distribution is similar for both LC-NA neuronal subpopulations. However, finer analysis demonstrated important differences in inputs from specific brain regions. Moreover, sex related differences were apparent, but only in inputs to amygdala-projecting LC-NA neurons. These findings reveal a cell type and sex specific afferent input organization which could allow for context dependent and target specific control of NA outflow to forebrain structures involved in emotional control and decision making.

neuroscience↗

bioRxiv2019

Episodic memory encoding by a place cell sub-population

Study of the hippocampal place cell system has greatly enhanced our understanding of memory encoding for distinct places, but how episodic memories for distinct experiences occurring within familiar environments are encoded is not clear. One possibility is that different place cell populations encode details of the novel experience or maintain the representation of the unchanged environment. We developed an aversive spatial decision making task which induced partial remapping in CA1, allowing us to identify both remapping and stable cell populations. We found that remapping cells exhibited distinct features not present in stable cells. During memory encoding, their theta phase preferences shifted to earlier phases, when CA3 inputs are strongest. Further, their recruitment into replay events increased during learning, unlike that of stable cells. Our demonstration of a sub-population of place cells identified on the basis of their degree of remapping and exhibiting unique changes in their spike firing properties with learning lend support to a model in which novel and familiar spatial/contextual information is encoded and maintained, respectively, by separate place cell populations.

neuroscience↗

bioRxiv2018

The Claustrum Coordinates Cortical Slow-Wave Activity

During sleep and awake rest, the neocortex generates large-scale slow-wave activity. Here we report that the claustrum, a poorly understood subcortical neural structure, coordinates neocortical slow-wave generation. We established a transgenic mouse line allowing genetic and electrophysiological interrogation of a subpopulation of claustral glutamatergic neurons. These claustral excitatory neurons received inputs from glutamatergic neurons in a large neocortical network. Optogenetic activation of claustral neurons in vitro induced excitatory post-synaptic responses in most neocortical neurons, but elicited action potentials primarily in inhibitory interneurons. Optogenetic activation of claustral neurons in vivo induced a Down-state featuring a prolonged silencing of neural acticity in all layers of many cortical areas, followed by a globally synchronized Down-to-Up state transition. These results demonstrate a crucial role of the claustrum in synchronizing inhibitory interneurons across the neocortex for spatiotemporal coordination of brain state. Thus, the claustrum is a major subcortical hub for the synchronization of neocortical slow-wave activity.

neuroscience↗