September 18: David Sulzer, Ph.D., Columbia University
Professor, Department of Neurology
"The Dopamine Synapse"
Faculty Host: Annette Fleckenstein, Dentistry
Student Host: Charlotte Magee
Research Summary: Our lab seeks to understand those synaptic connections in the cortex
and basal ganglia that underlie memory, learning, and behavior, and the mechanisms
underlying diseases that occur at these synapses, including Parkinson's Disease, schizophrenia,
autism, and drug addiction.
In particular, we explore synapses formed by the midbrain dopamine projections that
underlie "reward" and learning, including that associated with psychostimulant drugs,
food and sex, and voluntary motor control, and how they interact with inputs from
the cortex. These synapses are the primary target for drugs of abuse including cocaine,
amphetamine, nicotine, and opiates. Alterations in their state underlie addiction
and schizophrenic psychosis. The loss of the midbrain dopamine neurons is the cause
of Parkinson's disease, while the loss of their target neurons in the striatum causes
Huntington's disease. Our research further suggests that altered synaptic interactions
between the cortex and this system contributes to the pathology that underlies instances
of autism spectrum disorder.
October 16: Jennifer Li, Ph.D., Rowland Institute at Harvard
Rowland Junior Fellow
"Brain wide imaging of complex behaviors in freely swimming larval zebrafish "
Faculty Host: Adam Douglass, Neurobiology & Anatomy
Student Host: Ariadne Penalva
Research Summary: The ability to adjust one’s actions based on past experience (learning)
and retain the value of past actions (memory) is one of the most complex, fascinating,
and mysterious processes mediated by the animal brain. Fundamental questions remain
about the precise contribution of individual neurons to learning, as well as the nature
and complexity of interactions across neural circuits implicated in learning. Our
lab aims to address these questions by recording and manipulating activity throughout
an entire vertebrate brain while an animal actively engages in exploration and learning.
Using the latest advances in optogenetics and microscopy, we will identify and selectively
manipulate the neural circuitry that underlies learning in larval zebrafish, as well
as develop novel high throughput learning paradigms for pharmacological and genetic
screening.
November 20: Aaron Batista, Ph.D., University of Pittsburgh
Associate Professor, Department of Bioengineering
"Neural population mechanisms of learning"
Faculty Host: Chuck Dorval, Bioengineering
Student Host: Heidi Febinger
Research Summary: How does the brain change when we learn? Our approach to this perennial
question focuses on how populations of neurons change their patterns of coordination
to enable us to perform new skills. We do this using a brain-computer interface (BCI)
paradigm in which monkeys control a cursor on a computer screen by generating patterns
of activity across 90 or so neural units recorded in primary motor cortex. We are
finding that the brain employs different strategies to re-organize neural activity
at fast and slow timescales. I will conclude by arguing that our BCI approach enables
us to see neural mechanisms that are also at play during skill learning.
January 15: Bita Moghaddam, Ph.D., Oregon Health and Science University
Ruth Matarazzo Professor and Chair, Department of Behavioral Neuroscience
"Anxiety as a disorder of action computation by the prefrontal cortex"
Faculty Host: Kristen Keefe, Pharmacology & Toxicology
Student Host: Danielle Giangrasso
Research Summary: Neurobiological disorders that affect cognition and emotion are
the most prevalent and the most devastating of human disorders. Whether it is a chronic
disease such as schizophrenia or transient bouts of anxiety and panic attacks, they
influence every aspect of an individual’s life and produce enduring personal anguish
and hardship to family. New treatments for these conditions are contingent upon research
breakthroughs that explain the neuronal processes that support cognition and emotion.
By increasing our basic understanding of how these processes work, we can identify
genetic or environmental causes that disrupt them. It is then that we can find cures
or prevention strategies for these disorders.
The Moghaddam lab uses a systems approach to study the neuronal mechanisms that maintain cognitive and emotional functions in key brain regions that have been implicated in symptoms of schizophrenia, ADHD, anxiety, and addictive disorders. Our primary focus is on prefrontal cortex subregions and dopamine neurons in the midbrain.
We use electrophysiological and neurochemical methods to study the coordinated activity of these regions during various behavioral paradigms. Pharmacological or environmental manipulation of these systems is used to model variables that are relevant to disease. Our work so far has led to fundamental new conceptualization about the pathophysiology of schizophrenia and identified novel pharmacological approaches for treatment of this brain disease. New directions include characterization of these neuronal systems during adolescence. The onset of symptoms for most psychiatric disorders is during adolescence; therefore, understanding what goes awry in this developmental period is critical for defining the neuronal basis of the disease process and designing strategies that prevent the onset of symptoms.
February 19: Axel Brunger, Ph.D., Stanford University
Professor and HHMI Investigator, Department of Molecular & Cellular Physiology
"Molecular mechanisms of synaptic neurotransmitter release"
Faculty Host: Erik Jorgensen, Biology
Student Host: Jenifer Einstein
Research Summary: Nerve cells communicate by releasing the contents of neurotransmitter-bearing
synaptic vesicles into the space between adjoining cells. This process depends on
many proteins that promote vesicle and synaptic vesicle - plasma membrane fusion.
The Brunger lab uses structural and biophysical tools to capture this machinery at
different stages of vesicle fusion. These structures and functional data then provide
the framework for further investigations into the dynamic aspects of the system using
microscopy of reconstituted systems and neuronal cultures.
March 19: Patrick Kanold, Ph.D., University of Maryland, College Park
Professor, Department of Biology
"Circuits and plasticity in the developing auditory cortex: How you learned your mother’s
voice"
Faculty Host: Michael Deans, Otolaryngology, Surgery Division
Student Host: Evan Ratzan
Research Summary: The goal of the lab’s research is to understand how experiencing
and interacting with the world shapes our brains. Since audition is a key sense underlying
both human and animal communication we focus on the auditory system. The functional
representation of sounds is established during early development and is further shaped
by life experience and learning. We interrogate the changing sensory representations
in the auditory cortex, using in vivo and in vitro circuit mapping, large-scale multiphoton
imaging approaches, and computational analysis. I will discuss recent studies from
our lab that have started to explain the development, and rapid plasticity of auditory
cortex. Our results show that the developing auditory cortex contains specialized
circuits, formed by subplate neurons, that are responsive to sounds from the earliest ages
on. Thus, these neurons provide an early substrate for hearing experience before permanent
circuits are mature. We also find that some of these subplate neurons are retained into
adulthood. Consequently, early experience, before the traditional critical period,
can have a life-long impact.
April 16: Yun Zhang, Ph.D., Harvard University
Professor, Department of Organismic and Evolutionary Biology
Center for Brain Science
"Circuit mechanisms underlying olfactory learning"
Faculty Host: Villu Maricq, Neurobiology & Anatomy
Student Host: Pablo Maldonado
Research Summary: Learning is displayed as experience-dependent changes in sensorimotor
response. We study the property of the underlying neural circuit and how it changes
during learning. We have mapped the olfactory neural circuit that encodes the naive
or the learned behavioral response and have started to characterize the molecular
and cellular mechanisms governing the function of the neural circuits. For example,
our recent studies show that the complex activity in a C. elegans interneuron integrates the information of odorant and locomotory pattern to mediate
steering. Learning modulates the sensorimotor integration to alter odorant-guided
steering. Our results also characterize how training alters the properties of the
neural circuit that regulate other sensory-guided reorienting movements in a way that
is specific to the training stimulus. Together, our findings provide mechanistic insights
into how experience modulates information flow in a neural network to generate behavioral
alterations.