Publications by authors named "Robert Froemke"

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species.

View Article and Find Full Text PDF

Transcranial Ultrasound Stimulation (TUS) can noninvasively and reversibly perturb neuronal activity, but the mechanisms by which ultrasound engages brain circuits to induce functional effects remain unclear. To elucidate these interactions, we applied TUS to the cortex of awake mice and concurrently monitored local neural activity at the acoustic focus with two-photon calcium imaging. We show that TUS evokes highly focal responses in three canonical neuronal populations, with cell-type-specific dose dependencies.

View Article and Find Full Text PDF

Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS.

View Article and Find Full Text PDF

Neuronal responses during behavior are diverse, ranging from highly reliable 'classical' responses to irregular 'non-classically responsive' firing. While a continuum of response properties is observed across neural systems, little is known about the synaptic origins and contributions of diverse responses to network function, perception, and behavior. To capture the heterogeneous responses measured from auditory cortex of rodents performing a frequency recognition task, we use a novel task-performing spiking recurrent neural network incorporating spike-timing-dependent plasticity.

View Article and Find Full Text PDF

Introduction: Role-play, a key creative process in theatre, is used in therapeutic interventions to improve social skills, emotion regulation, and memory. Although role-play is widely used as a psychotherapeutic technique, its mechanisms of action are not fully understood.

Methods: Our study introduces a standardized controlled procedure for promoting role-play in the laboratory based on the portrayal of a fictional persona and examines its effects on anxiety, affect, prosocial attitudes, and salivary oxytocin dynamics in 38 participants.

View Article and Find Full Text PDF

Psychosocial and environmental factors, including loss of natural reward, contribute to the risk of drug abuse. Reward loss has been modeled in animals by removal from social or sexual contact, transfer from enriched to impoverished housing, or restriction of food. We previously showed that food restriction increases the unconditioned rewarding effects of abused drugs and the conditioned incentive effects of drug-paired environments.

View Article and Find Full Text PDF

A new study has identified the periaqueductal gray as an important brain region for play and tickle behavior in rats.

View Article and Find Full Text PDF

Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing. Suckling triggers the release of oxytocin, but other sensory cues-specifically, infant cries-can increase the levels of oxytocin in new human mothers, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons.

View Article and Find Full Text PDF

Aggression is an evolutionarily conserved behavior that controls social hierarchies and protects valuable resources like mates, food, and territory. In mice, aggressive behaviour can be broken down into an appetitive phase, which involves approach and investigation, and a consummatory phase, which involves biting, kicking, and wrestling. By performing an unsupervised weighted correlation network analysis on whole-brain c-Fos expression, we identified a cluster of brain regions including hypothalamic and amygdalar sub-regions and olfactory cortical regions highly co-activated in male, but not female aggressors (AGG).

View Article and Find Full Text PDF

Alzheimer's disease (AD) is characterized by neurodegeneration, memory loss, and social withdrawal. Brain inflammation has emerged as a key pathogenic mechanism in AD. We hypothesized that oxytocin, a pro-social hypothalamic neuropeptide with anti-inflammatory properties, could have therapeutic actions in AD.

View Article and Find Full Text PDF

Transactivating response region DNA binding protein 43 (TDP-43) pathology is prevalent in dementia, but the cell type-specific effects of TDP-43 pathology are not clear, and therapeutic strategies to alleviate TDP-43-linked cognitive decline are lacking. We found that patients with Alzheimer's disease or frontotemporal dementia have aberrant TDP-43 accumulation in hippocampal astrocytes. In mouse models, induction of widespread or hippocampus-targeted accumulation in astrocytic TDP-43 caused progressive memory loss and localized changes in antiviral gene expression.

View Article and Find Full Text PDF

Oxytocin is a neuropeptide critical for maternal physiology and social behavior, and is thought to be dysregulated in several neuropsychiatric disorders. Despite the biological and neurocognitive importance of oxytocin signaling, methods are lacking to activate oxytocin receptors with high spatiotemporal precision in the brain and peripheral mammalian tissues. Here we developed and validated caged analogs of oxytocin which are functionally inert until cage release is triggered by ultraviolet light.

View Article and Find Full Text PDF

Neurons in the prefrontal cortex (PFC) can provide top-down regulation of sensory-affective experiences such as pain. Bottom-up modulation of sensory coding in the PFC, however, remains poorly understood. Here, we examined how oxytocin (OT) signaling from the hypothalamus regulates nociceptive coding in the PFC.

View Article and Find Full Text PDF

Cochlear implants (CIs) are neuroprosthetic devices that can provide hearing to deaf people. Despite the benefits offered by CIs, the time taken for hearing to be restored and perceptual accuracy after long-term CI use remain highly variable. CI use is believed to require neuroplasticity in the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to the variability in outcomes.

View Article and Find Full Text PDF

Brain-derived Neurotrophic Factor (BDNF) binds to the TrkB tyrosine kinase receptor, which dictates the sensitivity of neurons to BDNF. A unique feature of TrkB is the ability to be activated by small molecules in a process called transactivation. Here we report that the brain neuropeptide oxytocin increases BDNF TrkB activity in primary cortical neurons and in the mammalian neocortex during postnatal development.

View Article and Find Full Text PDF

Social interactions powerfully impact the brain and the body, but high-resolution descriptions of these important physical interactions and their neural correlates are lacking. Currently, most studies rely on labor-intensive methods such as manual annotation. Scalable and objective tracking methods are required to understand the neural circuits underlying social behavior.

View Article and Find Full Text PDF

Objective: This study's aims were to refine Music Upper Limb Therapy-Integrated (MULT-I) to create a feasible enriched environment for stroke rehabilitation and compare its biologic and behavioral effects with that of a home exercise program (HEP).

Design: This was a randomized mixed-methods study of 30 adults with post-stroke hemiparesis. Serum brain-derived neurotrophic factor and oxytocin levels measured biologic effects, and upper limb function, disability, quality of life, and emotional well-being were assessed as behavioral outcomes.

View Article and Find Full Text PDF

Social interaction deficits seen in psychiatric disorders emerge in early-life and are most closely linked to aberrant neural circuit function. Due to technical limitations, we have limited understanding of how typical versus pathological social behavior circuits develop. Using a suite of invasive procedures in awake, behaving infant rats, including optogenetics, microdialysis, and microinfusions, we dissected the circuits controlling the gradual increase in social behavior deficits following two complementary procedures-naturalistic harsh maternal care and repeated shock alone or with an anesthetized mother.

View Article and Find Full Text PDF

Maternal care, including by non-biological parents, is important for offspring survival. Oxytocin, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress.

View Article and Find Full Text PDF

Oxytocin regulates parturition, lactation, parental nurturing, and many other social behaviors in both sexes. The circuit mechanisms by which oxytocin modulates social behavior are receiving increasing attention. Here, we review recent studies on oxytocin modulation of neural circuit function and social behavior, largely enabled by new methods of monitoring and manipulating oxytocin or oxytocin receptor neurons in vivo.

View Article and Find Full Text PDF
Article Synopsis
  • Vagus nerve stimulation (VNS) can help reduce inflammation and autoimmune diseases based on studies done on mice and humans.
  • Researchers created a way to use VNS for a long time in mice, and it worked well, with many mice showing good heart rate changes over four weeks.
  • This method helps scientists learn more about the vagus nerve and could be helpful for treating long-lasting diseases in mice.
View Article and Find Full Text PDF

Integration of social cues to initiate adaptive emotional and behavioral responses is a fundamental aspect of animal and human behavior. In humans, social communication includes prominent nonverbal components, such as social touch, gestures and facial expressions. Comparative studies investigating the neural basis of social communication in rodents has historically been centered on olfactory signals and vocalizations, with relatively less focus on non-verbal social cues.

View Article and Find Full Text PDF