Laboratory for Understanding the Physiology of Neuropeptides in Developing, Adult & Aging Circuits

The Laboratory for Understanding the Physiology of Neuropeptides in Developing, Adult and Aging Circuits at the Psychiatry Research Institute at Montefiore Einstein (PRIME) explores how neuromodulation and inhibition shape brain circuits related to social communication and motor function. Research focuses on the dynamic modulation of GABAergic inhibition, synaptic plasticity and circuit development to better understand complex behaviors. Our research has broad implications for neurodevelopmental and neurodegenerative disorders, and our ultimate goal is to understand better how context-dependent modulation of cerebellar function controls motor behavior, cognition and emotion in health and disease.

As we navigate the world, we are constantly confronted with a wealth of sensory information that we have to detect, integrate and filter to generate an appropriate behavioral response. How we respond requires the interplay of numerous brain regions and depends on many factors, including the context in which a sensory stimulus occurred, previous experiences and internal state.

The cellular and molecular correlates for these external and internal factors include the release of context-dependent neuromodulators, altered neuronal activity, synaptic plasticity and gene expression. On a circuit level, these mechanisms regulate the local integration of information on varying time scales and ultimately control output to other brain regions. In the Rudolph Laboratory, we aim to identify the molecular, cellular and circuit mechanisms that allow the cerebellum, an area of the brain that receives rich multisensory input, to respond to physiological context dynamically. We focus on the neuromodulatory systems involved in autonomic and metabolic regulation, social interactions and sex-specific signaling. Using genetic and viral approaches, electrophysiology and behavioral testing, we examine the anatomical and molecular basis of neuromodulation in the mouse cerebellum, identify the circuit elements that respond to modulatory signals and explain how this alters cerebellar output.

Our research focuses on the following areas:

The Social Cerebellum

In determining which circuits allow the cerebellum to control emotion, cognition and adaptive learning, we combine mouse genetics, virus-based circuit mapping, optogenetics, electrophysiology and behavioral testing to understand how the cerebellum and its inputs and outputs control social and affective behaviors.

Inhibition & Neuromodulation

The striking diversity in cellular composition, region-specific connectivity and neuromodulatory input suggests that the cerebellum is subdivided into functionally specialized regions. We aim to explain how inhibitory interneurons and context-dependent neuromodulators shape excitability and synaptic transmission in specialized regions to adapt cerebellar function to physiological challenges such as stress and social interaction.

Neurodevelopmental Disorders

Cerebellar dysfunction is a hallmark of many neurodevelopmental and psychiatric disorders, including autism spectrum disorders (ASDs), attention-deficit/hyperactivity disorder (ADHD), schizophrenia, depression and anxiety. We examine the factors that promote and disrupt circuit maturation of the cerebellum in health and disease.

Our team is actively involved in clinical research, evaluations and collaborations. Current projects at the laboratory include the following areas of research:

Neuropeptide Signaling in the Cerebellar Cortex

The cerebellum partakes in a range of cognitive-affective and motor functions that require dynamic adaptation of circuit processing. This project employs transcriptomics and electrophysiology to better understand how the neuropeptides oxytocin and vasopressin regulate GABAergic inhibition and the integration of sensory information in the cerebellar cortex.

Neuropeptide Signaling Through the Cerebrospinal Fluid

Neuropeptides modulate circuits across the brain but are often not released near their target receptors. This project seeks to explain how cerebrospinal fluid propagates neuropeptides and how this mode of communication affects behavioral choice. We answer these questions using in vivo two-photon imaging, viral tracing and click chemistry tools.

The Role of Oxytocin in Cerebellar Development

Brief neuromodulatory events in early development can profoundly shape circuit maturation and behavior. This project explores how oxytocin shapes the development of the cerebellar cortex and the emergence of cerebellum-dependent behaviors.