BRANDON
LABORATORY
Navigation
Navigation is an essential cognitive skill, guiding us seamlessly through the environment. Our laboratory's research is dedicated to unraveling the complexities of this skill, which relies on sophisticated neural circuitry spanning subcortical to cortical regions. Despite its critical role in everyday functioning, navigation is one of the first abilities compromised by neurodegenerative conditions like Alzheimer's disease, leading to disorientation and distress. Our work seeks to understand these processes in their entirety, aiming to shed light on the broader neural underpinnings of cognition and inform strategies to preserve orientation capabilities in vulnerable populations.
Memory
Memory is the tapestry of our identity, seamlessly encoding, retaining, and retrieving the myriad details that make up our daily lives. This intricate system allows us to learn from the past, adapt to the present, and plan for the future. However, this effortless process is vulnerable to the effects of aging, with conditions like dementia and Alzheimer's disease highlighting the fragility of our cognitive archives. Our research delves into the mechanisms of memory, seeking to understand and mitigate the decline that can dim the vividness of our personal narratives as we age.
Alzheimer's disease
Alzheimer's Disease represents one of the most significant challenges to cognitive health in the aging population, characterized by a progressive decline in memory and spatial navigation. Our laboratory employs advanced genetically engineered mouse models to replicate the hallmark pathologies of Alzheimer's, providing a window into the deteriorating neural systems. Through meticulous study of these models, we aim to pinpoint the disruptions within the brain's memory and navigation circuits. Understanding the intricacies of these impairments is the first step toward our ultimate goal: devising therapeutic strategies to repair and restore cognitive functions, thereby reorienting and reconnecting individuals with Alzheimer's to the world around them.
Research Themes
OUR RESEARCH
Research Themes
Navigation is an essential cognitive skill, guiding us seamlessly through the environment. Our laboratory's research is dedicated to unraveling the complexities of this skill, which relies on sophisticated neural circuitry spanning subcortical to cortical regions. Despite its critical role in everyday functioning, navigation is one of the first abilities compromised by neurodegenerative conditions like Alzheimer's disease, leading to disorientation and distress. Our work seeks to understand these processes in their entirety, aiming to shed light on the broader neural underpinnings of cognition and inform strategies to preserve orientation capabilities in vulnerable populations.
Memory is the tapestry of our identity, seamlessly encoding, retaining, and retrieving the myriad details that make up our daily lives. This intricate system allows us to learn from the past, adapt to the present, and plan for the future. However, this effortless process is vulnerable to the effects of aging, with conditions like dementia and Alzheimer's disease highlighting the fragility of our cognitive archives. Our research delves into the mechanisms of memory, seeking to understand and mitigate the decline that can dim the vividness of our personal narratives as we age.
Alzheimer's Disease represents one of the most significant challenges to cognitive health in the aging population, characterized by a progressive decline in memory and spatial navigation. Our laboratory employs advanced genetically engineered mouse models to replicate the hallmark pathologies of Alzheimer's, providing a window into the deteriorating neural systems. Through meticulous study of these models, we aim to pinpoint the disruptions within the brain's memory and navigation circuits. Understanding the intricacies of these impairments is the first step toward our ultimate goal: devising therapeutic strategies to repair and restore cognitive functions, thereby reorienting and reconnecting individuals with Alzheimer's to the world around them.
"Somewhere, something incredible is waiting to be known."
Carl Sagan
In vivo electrophysiology is a key technique in neuroscience, enabling the real-time monitoring of neuronal activities, with single-neuron resolution, in animals as they display natural behaviors. It's instrumental in exploring the neural dynamics during various behaviors and observing changes in conditions like Alzheimer's disease.
In vivo calcium imaging allows the observation of large groups of neurons in behaving animals, offering insights into brain function over time and in conditions like Alzheimer's. Using devices like miniscopes, it tracks individual neuron activity for weeks, shedding light on learning, memory, and disease progression at a cellular level.
Fiber photometry tracks population-level brain activity by monitoring calcium or neurotransmitter levels, providing insights into neural circuit dynamics during behavior. It involves implanting optical fibers to measure fluorescence in specific brain areas, making it a vital tool for long-term in vivo studies.
Optogenetics merges genetics and optics to manipulate and observe neurons in living animals with high precision. By introducing light-sensitive proteins into specific neurons, researchers can control neural activity with light, uncovering the direct links between brain activity and behavior.
Chemogenetics, especially using DREADDs, allows precise control of neuronal activity in animals by introducing engineered receptors responsive to specific synthetic ligands. This method enables targeted, reversible manipulation of brain dynamics, aiding in the study of complex behaviors and diseases without the need for light activation, providing a unique approach in neuroscience research.
Rabies-mediated monosynaptic circuit tracing uses a modified rabies virus to map direct neural connections in the brain. By infecting designated starter neurons and spreading retrogradely to connected neurons, this technique provides a precise map of the brain's synaptic pathways, essential for understanding complex neural networks.
Transgenic mouse models play a crucial role in neuroscience, particularly in Alzheimer's disease research and cell-specific studies. They enable the replication of disease traits like amyloid-β plaques and tau tangles for understanding Alzheimer's pathology and testing treatments, despite challenges in mimicking human pathology fully. Additionally, models using Cre-expressing lines allow precise gene manipulation in specific neuron types, facilitating targeted studies on neural functions and disorders, significantly advancing our understanding of complex neurological conditions.
In computational neuroscience, my lab uses modeling to predict and interpret data, aiming for a balance between simplicity and biological realism. One focus is on Continuous Attractor Based Models of the Head Direction System, capturing how the brain maintains spatial orientation. Another aspect involves refining existing models with new data, ensuring they accurately reflect neural dynamics. This approach avoids overfitting and enhances the models' broad applicability, making them valuable for hypothesis testing and exploring fundamental neuroscience questions.
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Technology
In Vivo Electrophysiology
In vivo electrophysiology is a key technique in neuroscience, enabling the real-time monitoring of neuronal activities, with single-neuron resolution, in animals as they display natural behaviors. It's instrumental in exploring the neural dynamics during various behaviors and observing changes in conditions like Alzheimer's disease.
In Vivo Calcium Imaging
In vivo calcium imaging allows the observation of large groups of neurons in behaving animals, offering insights into brain function over time and in conditions like Alzheimer's. Using devices like miniscopes, it tracks individual neuron activity for weeks, shedding light on learning, memory, and disease progression at a cellular level.
Fiber Photometry
Fiber photometry tracks population-level brain activity by monitoring calcium or neurotransmitter levels, providing insights into neural circuit dynamics during behavior. It involves implanting optical fibers to measure fluorescence in specific brain areas, making it a vital tool for long-term in vivo studies.
Optogenetics
Optogenetics merges genetics and optics to manipulate and observe neurons in living animals with high precision. By introducing light-sensitive proteins into specific neurons, researchers can control neural activity with light, uncovering the direct links between brain activity and behavior.
Chemogenetics
Chemogenetics, especially using DREADDs, allows precise control of neuronal activity in animals by introducing engineered receptors responsive to specific synthetic ligands. This method enables targeted, reversible manipulation of brain dynamics, aiding in the study of complex behaviors and diseases without the need for light activation, providing a unique approach in neuroscience research.
Rabies Mediated Retrograde Circuit Tracing
Rabies-mediated monosynaptic circuit tracing uses a modified rabies virus to map direct neural connections in the brain. By infecting designated starter neurons and spreading retrogradely to connected neurons, this technique provides a precise map of the brain's synaptic pathways, essential for understanding complex neural networks.
Transgenic Mouse Models
Transgenic mouse models play a crucial role in neuroscience, particularly in Alzheimer's disease research and cell-specific studies. They enable the replication of disease traits like amyloid-β plaques and tau tangles for understanding Alzheimer's pathology and testing treatments, despite challenges in mimicking human pathology fully. Additionally, models using Cre-expressing lines allow precise gene manipulation in specific neuron types, facilitating targeted studies on neural functions and disorders, significantly advancing our understanding of complex neurological conditions.
Computational Modeling
In computational neuroscience, my lab uses modeling to predict and interpret data, aiming for a balance between simplicity and biological realism. One focus is on Continuous Attractor Based Models of the Head Direction System, capturing how the brain maintains spatial orientation. Another aspect involves refining existing models with new data, ensuring they accurately reflect neural dynamics. This approach avoids overfitting and enhances the models' broad applicability, making them valuable for hypothesis testing and exploring fundamental neuroscience questions.