Emergence and fragmentation of the alpha-band driven by neuronal network dynamics

Rhythmic neuronal network activity underlies brain oscillations. To investigate how connected neuronal networks contribute to the emergence of the α-band and to the regulation of Up and Down states, we study a model based on synaptic short-term depression-facilitation with afterhyperpolarization (AHP). We found that the α-band is generated by the network behavior near the attractor of the Up-state. Coupling inhibitory and excitatory networks by reciprocal connections leads to the emergence of a stable α-band during the Up states, as reflected in the spectrogram. To better characterize the emergence and stability of thalamocortical oscillations containing α and δ rhythms during anesthesia, we model the interaction of two excitatory networks with one inhibitory network, showing that this minimal topology underlies the generation of a persistent α-band in the neuronal voltage characterized by dominant Up over Down states. Finally, we show that the emergence of the α-band appears when external inputs are suppressed, while fragmentation occurs at small synaptic noise or with increasing inhibitory inputs. To conclude, α-oscillations could result from the synaptic dynamics of interacting excitatory neuronal networks with and without AHP, a principle that could apply to other rhythms.

The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

Communication between the mediodorsal thalamus and prelimbic cortex regulates timing performance in rats

Predicting when future events will occur and adjusting behavior accordingly is critical to adaptive behavior. Despite this, little is known about the brain networks that encode time and how this ultimately impacts decision-making. One established finding is that the prefrontal cortex (PFC) and its non-human analogues (e.g., the rodent prelimbic cortex; PL) mediate timing. This provides a starting point for exploring the networks that support temporal processing by identifying areas that interact with the PFC during timing tasks. For example, substantial work has explored the role of frontostriatal circuits in timing. However, other areas are undoubtedly involved. The mediodorsal nucleus of the thalamus (MD) is an excellent candidate region. It shares dense, reciprocal connections with PFC-areas in both humans and non-human species and is implicated in cognition. However, causal data implicating MD-PFC interactions in cognition broadly is still sparse, and their role in timing specifically is currently unknown. To address this, we trained male rats on a time-based, decision-making task referred to as the 'peak-interval' procedure. During the task, presentation of a cue instructed the rats to respond after a specific interval of time elapsed (e.g., tone-8 seconds). We incorporated two cues; each requiring a response after a distinct time-interval (e.g., tone-8 seconds / light-16 seconds). We tested the effects of either reversibly inactivating the MD or PL individually or functionally disconnecting them on performance. All manipulations caused a comparable timing deficit. Specifically, responses showed little organization in time, as if primarily guided by motivational systems. These data expand our understanding of the networks that support timing and suggest that MD-PL interactions specifically are a core component. More broadly, our results suggest that timing tasks provide a reliable assay for characterizing the role of MD-PL interactions in cognition using rodents, which has been difficult to establish in the past.

The Medial Septum as a Potential Target for Treating Brain Disorders Associated with Oscillopathies

The medial septum (MS), as part of the basal forebrain, supports many physiological functions, from sensorimotor integration to cognition. With often reciprocal connections with a broad set of peers at all major divisions of the brain, the MS orchestrates oscillatory neuronal activities throughout the brain. These oscillations are critical in generating sensory and emotional salience, locomotion, maintaining mood, supporting innate anxiety, and governing learning and memory. Accumulating evidence points out that the physiological oscillations under septal influence are frequently disrupted or altered in pathological conditions. Therefore, the MS may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. Recent studies have revealed that the patterned stimulation of the MS alleviates symptoms of epilepsy. We discuss here that stimulus timing is a critical determinant of treatment efficacy on multiple time scales. On-demand stimulation may dramatically reduce side effects by not interfering with normal physiological functions. A precise pattern-matched stimulation through adaptive timing governed by the ongoing oscillations is essential to effectively terminate pathological oscillations. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders including Alzheimer’s disease, anxiety/fear, schizophrenia, and depression, as well as pain.

The Thalamus as a Blackboard for Perception and Planning

It has been suggested that the thalamus acts as a blackboard, on which the computations of different cortical modules are composed, coordinated, and integrated. This article asks what blackboard role the thalamus might play, and whether that role is consistent with the neuroanatomy of the thalamus. It does so in a context of Bayesian belief updating, expressed as a Free Energy Principle. We suggest that the thalamus-as-a-blackboard offers important questions for research in spatial cognition. Several prominent features of the thalamus—including its lack of olfactory relay function, its lack of internal excitatory connections, its regular and conserved shape, its inhibitory interneurons, triadic synapses, and diffuse cortical connectivity—are consistent with a blackboard role.Different thalamic nuclei may play different blackboard roles: (1) the Pulvinar, through its reciprocal connections to posterior cortical regions, coordinates perceptual inference about “what is where” from multi-sense-data. (2) The Mediodorsal (MD) nucleus, through its connections to the prefrontal cortex, and the other thalamic nuclei linked to the motor cortex, uses the same generative model for planning and learning novel spatial movements. (3) The paraventricular nucleus may compute risk-reward trade-offs. We also propose that as any new movement is practiced a few times, cortico-thalamocortical (CTC) links entrain the corresponding cortico-cortical links, through a process akin to supervised learning. Subsequently, the movement becomes a fast unconscious habit, not requiring the MD nucleus or other thalamic nuclei, and bypassing the thalamic bottleneck.

Structural Spine Plasticity in Olfaction: Memory and Forgetting, Enhanced vs. Reduced Discriminability after Learning

How animals learn to discriminate between different sensory stimuli is an intriguing question. An important, common step towards discrimination is the enhancement of differences between the representations of relevant stimuli. This can be part of the learning process. In rodents, the olfac-tory bulb, which is known to contribute to this pattern separation, exhibits extensive structural synaptic plasticity even in adult animals: reciprocal connections between excitatory mitral cells and inhibitory granule cells are persistently formed and eliminated, correlated with mitral cell and granule cell activity. Here we present a Hebbian-type model for this plasticity. It captures the experimental observation that the same learning protocol that enhanced the discriminability of similar stimuli actually reduced that of dissimilar stimuli. The model predicts that the learned bulbar network structure is remembered across training with additional stimuli, unless the new stimuli interfere with the representations of previously learned ones.

Safe but Lonely? Loneliness, Anxiety, and Depression Symptoms and COVID-19

BackgroundThe COVID-19 pandemic has led governments worldwide to implement unprecedented response strategies. While crucial to limiting the spread of the virus, “social distancing” may lead to severe psychological consequences, especially in lonely individuals.MethodsWe used cross-sectional (n = 380) and longitudinal (n = 74) designs to investigate the links between loneliness, anxiety, and depression symptoms (ADS) and COVID-19 risk perception and affective response in young adults who implemented social distancing during the first 2 weeks of the state of epidemic threat in Poland.ResultsLoneliness was correlated with ADS and with affective response to COVID-19’s threat to health. However, increased worry about the social isolation and heightened risk perception for financial problems was observed in lonelier individuals. The cross-lagged influence of the initial affective response to COVID-19 on subsequent levels of loneliness was also found.ConclusionThe reciprocal connections between loneliness and COVID-19 response may be of crucial importance for ADS during the COVID-19 crisis.

The claustrum-medial prefrontal cortex network controls attentional set-shifting

SUMMARYIn various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.

Complement factor C1q mediates chronic neuron loss and inflammation post-brain injury

ABSTRACTWhile traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of cortical injury that does not directly damage subcortical structures, we found a chronic increase in C1q expression specifically in the corticothalamic circuit. Increased C1q expression co-localized with neuron loss and chronic inflammation, and correlated with altered cortical rhythms. Blocking C1q counteracted most of these outcomes, suggesting that C1q is a disease modifier in TBI. Since the corticothalamic circuit is important for sensory processing, attention, cognition, and sleep, all of which can be impaired by TBI, this circuit could be a new target for treating TBI-related disabilities.

Neuronal circuitry underlying female aggression in Drosophila

Aggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism’s internal state. While both sexes exhibit aggression, its neuronal underpinnings are understudied in females. Here, we describe a set of connected neurons in the adult Drosophila melanogaster central brain that drive female aggression. We identified a population of sexually dimorphic aIPg neurons whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated pC1d and aIPg neurons as core nodes regulating female aggression. pC1d activation increased female aggression and electron microscopy (EM) connectomic analysis demonstrated that aIPg neurons and pC1d have strong reciprocal connections. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.