Biology subjects

Wang, D. V.

Publications and source records attributed to Wang, D. V..

9 recordsLinked to original sources

bioRxiv2025

A cortical-hippocampal communication undergoes rebalancing after new learning

The brains ability to consolidate a wide range of memories while maintaining their distinctiveness across experiences remains poorly understood. Sharp-wave ripples, neural oscillations that occur predominantly within CA1 of the hippocampus during immobility and sleep, have been shown to play a critical role in the consolidation process. More recently, evidence has uncovered functional heterogeneity of pyramidal neurons within distinct sublayers of CA1 that display unique properties during ripples, potentially contributing to memory specificity. Despite this, it remains unclear exactly how ripples shift the activity of CA1 neuronal populations to accommodate the consolidation of specific memories and how sublayer differences manifest. Here, we studied interactions between the anterior cingulate cortex (ACC) and CA1 neurons during ripples and discovered a reorganization of their communication following learning. Specifically, using a generalized linear model decoder, we demonstrated the pre-existence of ACC-to-CA1 communication, which is weakened during post-training sleep following learning, suggesting that ACC activity reallocates the contribution of CA1 neurons during memory formation. Interestingly, the reorganization appeared unique for a subset of CA1 superficial (CA1sup) neurons that were task inactive, whereas communication between the ACC and CA1 deep neurons remained largely stable across pre- and post-training sleep. Consistent with this sublayer-selective reorganization, we found that optogenetic stimulations of the ACC preferentially suppressed CA1sup neurons while activating a unique subset of CA1 interneurons. Overall, these findings highlight an important role of the ACC in rebalancing CA1 neuronal populations contribution in learning and memory consolidation.

neuroscience↗

bioRxiv2025

Anterior cingulate cortex in complex associative learning: monitoring action state and action content

Environmental changes necessitate adaptive responses, and thus the ability to monitor ones actions and their connection to specific cues and outcomes is crucial for survival. The anterior cingulate cortex (ACC) is implicated in these processes, yet its precise role in action monitoring versus outcome tracking remains unclear. To investigate this, we developed a novel discrimination-avoidance task for mice, designed with clear temporal separation between actions and outcomes. Our findings show that ACC neurons primarily encode post-action variables over extended periods, reflecting the animals preceding actions rather than the outcomes or values of those actions. Specifically, we identified two distinct subpopulations of ACC neurons: one encoding the action state (whether an action was taken) and the other encoding the action content (which action was taken). Importantly, increased post-action ACC activity was associated with better performance in subsequent trials. These findings suggest that the ACC supports complex associative learning through extended signaling of rich action-relevant information, thereby bridging cue, action, and outcome associations.

neuroscience↗

bioRxiv2024

A distinct down state assembly in retrosplenial cortex during slow-wave sleep

Understanding the intricate mechanisms underlying slow-wave sleep (SWS) is crucial for deciphering the brains role in memory consolidation and cognitive functions. It is well-established that cortical delta oscillations (0.5-4 Hz) coordinate communications among various cortical, hippocampal, and thalamic regions during SWS. These delta oscillations have periods of Up and Down states, with the latter previously thought to represent complete cortical silence; however, new evidence suggests that Down states serve important functions for information exchange during memory consolidation. The retrosplenial cortex (RSC) stands out for its pivotal role in memory consolidation due to its extensive connectivity with memory-associated regions, although it remains unclear how RSC neurons engage in delta-associated consolidation processes. Here, we employed multi-channel in vivo electrophysiology to study RSC neuronal activity in freely behaving mice during natural SWS. We discovered that the RSC contains a discrete assembly of putative excitatory neurons ([~]20%) that initiated firing at SWS Down states and reached maximal firing at the Down-to-Up transitions. Therefore, we termed these RSC neurons the Down state assembly (DSA), and the remaining RSC excitatory neurons as non-DSA. Compared to non-DSA, DSA neurons exhibit a higher firing rate, larger cell body size, and no connectivity with nearby RSC neurons. Subsequently, we investigated RSC neuronal activity during a contextual fear conditioning paradigm and found that both DSA and non-DSA neurons exhibited increased firing activity during post-training sleep compared to pre-training sleep, indicating their roles in memory consolidation. Lastly, optogenetics combined with electrophysiology revealed that memory-associated inputs differentially innervated RSC excitatory neurons. Collectively, these findings provide insight on distinct RSC neuronal subpopulation activity in sleep and memory consolidation.

neuroscience↗

bioRxiv2023

Emerging many-to-one weighted mapping in hippocampus-amygdala network underlies memory formation

Memories are crucial for our daily lives, yet the network-level organizing principle that governs neural representations of our experiences remains to be determined. Employing dual-site electrophysiology recording in freely behaving mice, we discovered that hippocampal dorsal CA1 (dCA1) and basolateral amygdala (BLA) utilize distinct coding strategies to represent novel experiences. A small assembly of BLA neurons rapidly emerged during memory acquisition and remained active during subsequent consolidation, whereas the majority of dCA1 neurons engaged in the same processes. Machine learning decoding revealed that dCA1 population spikes predicted the BLA assembly firing rate. This suggests that most dCA1 neurons concurrently index an episodic event by rapidly establishing weighted communications with a specific BLA assembly, a process we call "many-to-one weighted mapping." Furthermore, we demonstrated that closed-loop optoinhibition of BLA activity triggered by dCA1 ripples after new learning resulted in impaired memory. These findings highlight a new principle of hippocampus-amygdala communication underlying memory formation and provide new insights into how the brain creates and stores memories.

neuroscience↗

bioRxiv2020

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

How does the prefrontal cortex (PFC) regulate motivated behavior? Our experiments characterize the circuits of the PFC regulating motivation, reinforcement and dopamine activity, revealing a novel cortico-thalamic loop. The stimulation of medial PFC (mPFC) neurons activated many downstream regions, as shown by functional MRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. Reciprocal excitatory functional connectivity, as well as co-activation of the two regions, was found in human participants who watched reinforcing videos. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement and dopaminergic neuron activity.

neuroscience↗

bioRxiv2020

Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction

The supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to illuminate how SuM neurons mediate such effects. The excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by the projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway is important in reinforcement and approach motivation and may play an important role in mood and substance-use disorders.

neuroscience↗

bioRxiv2020

Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition

Learning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we employed an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory expression and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.

neuroscience↗

bioRxiv2020

Encoding Fear of Heights by Basolateral Amygdala Neurons

Fear of heights is evolutionarily important for survival, yet it is unclear how and which brain regions encode such height threats. Given the importance of the basolateral amygdala (BLA) in processing both learned and innate fear, we investigated how BLA neurons may respond to high place exposure in freely behaving mice. We found that a discrete set of BLA neurons exhibited robust firing increases when the mouse was either exploring or placed on a high place, accompanied by increased heart rate and freezing. Importantly, these high-place fear neurons were only activated under height threats but not mild anxiogenic conditions. Furthermore, after a fear conditioning procedure, these high-place fear neurons developed conditioned responses to the context, but not the cue, indicating a convergence in encoding of dangerous/risky contextual information. Our results provide insights into the neural representation of the fear of heights and may have implications for treatment of excessive fear disorders.

neuroscience↗

bioRxiv2020

Midbrain dopamine neurons encode internal effort signal

Midbrain dopamine neurons of the ventral tegmental area (VTA) play a central role in both positive and negative motivation. As motivation and effort are intrinsically connected, we asked how the VTA dopamine neurons may also process internally driven effort signal. We designed two novel jumping tasks, the reward- and escape-motivated jumps, and revealed that the VTA dopamine neurons exhibit an effort-correlated activation during both jumping behaviors.

neuroscience↗