Andrea Hasenstaub, PhD

Associate Professor
Otolaryngology

Andrea Hasenstaub, PhD, is an Associate Professor in the Coleman Memorial Laboratories in the Department of Otolaryngology-Head and Neck Surgery (OHNS) at the University of California, San Francisco. She received her BS in Mathematics and Engineering at the California Institute of Technology in Pasadena, California; a M.Phil. in Biological Anthropology from Cambridge University, England; and a PhD in Neurobiology at Yale University in New Haven, Connecticut, followed by a fellowship at the Salk Institute in La Jolla, California.

Dr. Hasenstaub’s research is focused on understanding the genetic, cellular, and network operation of specific cell types in the mouse and human auditory cortex. One line of research focuses on inhibitory microcircuitry in normal and diseased brains. Within the cortex, diverse types of local circuit inhibitory neuron play vital roles in regulating and timing activity, and are key mediators of long-term developmental plasticity. Central auditory processing disorders, such as hyperacusis or tinnitus, may result in part from failure of cortical inhibitory networks to properly control the strength, timing, or plasticity of excitatory activity. These neurons' dysfunction is also implicated in broader neurodevelopmental disorders including schizophrenia, autism, epilepsy, and bipolar disorder. Treatments for these common and devastating diseases will require both a conceptual understanding of cortical interneurons' circuit functions, and a mechanistic understanding of their interactions.

Exciting advances in optical and genetic technology now bring this understanding within reach, by allowing us to systematically measure and manipulate properties of specific cell populations to answer basic questions about their function. Under what conditions are different kind of cortical neuron engaged? What computations do different types of neurons enable? How does each type's activation affect input integration in its targets? How can long-range or neuromodulatory inputs dynamically regulate these interactions, and how does this match moment-to-moment changes in cognitive or behavioral requirements? And what can we infer about design principles common to all neural systems, by studying the biophysical strategies interneurons adopt to fill these circuit roles?

A second line of research focuses on electrophysiological and genetic studies of human cerebral cortex. The majority of our information about cortical microcircuitry has been derived from studies in model systems, particularly mice, rats, ferrets, and cats. These studies have provided fundamental insight into the many aspects of cortical organization which are conserved across species. However, human neocortex differs from that of model systems in numerous ways including the presence of additional neuron types, specializations in conserved neuron types, altered patterns of local and long-range connections, and the presence of additional cytoarchitectonic areas. These evolutionarily recent specializations underlie the differences in cognitive capacity in humans compared to other species. By studying temporal and frontal cortex acutely resected from human surgical patients, we gain direct access to the cellular mechanisms of human brain function and disease, including the numerous human-specific aspects of cortical organization which cannot be directly studied in model systems.

Our overall goal is to identify the conditions under which different kinds of cortical neuron are engaged, understand what computations they enable cortical networks to perform, and establish the biophysical and circuit mechanisms by which they allow these computations to occur. We hope that this will guide us in developing a low-level mechanistic understanding of how their plasticity in aging, hearing loss, and other types of brain injury underlies the functional losses observed in these conditions.

Specialty:
Auditory physiology; central auditory processing

Expertise:
In vivo and in vitro recordings, mouse neurophysiology, human neurophysiology

Professional interests:
Hearing; auditory cortex; thalamus; cross-modal and modulatory influences; cell type specificity; comparative studies

Education:
• BS: California Institute of Technology, Mathematics and Engineering
• M. Phil.: Cambridge University, Biological Anthropology
• MS and PhD: Yale University, Neurobiology

Publications: 

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

Science (New York, N.Y.)

Paredes MF, Mora C, Flores-Ramirez Q, Cebrian-Silla A, Del Dosso A, Larimer P, Chen J, Kang G, Gonzalez Granero S, Garcia E, Chu J, Delgado R, Cotter JA, Tang V, Spatazza J, Obernier K, Ferrer Lozano J, Vento M, Scott J, Studholme C, Nowakowski TJ, Kriegstein AR, Oldham MC, Hasenstaub A, Garcia-Verdugo JM, Alvarez-Buylla A, Huang EJ

Clustered gamma-protocadherins regulate cortical interneuron programmed cell death.

eLife

Mancia Leon WR, Spatazza J, Rakela B, Chatterjee A, Pande V, Maniatis T, Hasenstaub AR, Stryker MP, Alvarez-Buylla A

Transplanted cells are essential for the induction but not the expression of cortical plasticity.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Hoseini MS, Rakela B, Flores-Ramirez Q, Hasenstaub AR, Alvarez-Buylla A, Stryker MP

Vesicular GABA transporter is necessary for transplant-induced critical period plasticity in mouse visual cortex.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Priya R, Rakela B, Kaneko M, Spatazza J, Larimer P, Hoseini MS, Hasenstaub AR, Alvarez-Buylla A, Stryker MP

Secretagogin is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity.

Cerebral cortex (New York, N.Y. : 1991)

Raju CS, Spatazza J, Stanco A, Larimer P, Sorrells SF, Kelley KW, Nicholas CR, Paredes MF, Lui JH, Hasenstaub AR, Kriegstein AR, Alvarez-Buylla A, Rubenstein JL, Oldham MC

Visual Information Present in Infragranular Layers of Mouse Auditory Cortex.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Morrill RJ, Hasenstaub AR

Amplitude modulation coding in awake mice and squirrel monkeys.

Journal of neurophysiology

Hoglen NEG, Larimer P, Phillips EAK, Malone BJ, Hasenstaub AR

Cortical Interneurons Differentially Regulate the Effects of Acoustic Context.

Cell reports

Phillips EAK, Schreiner CE, Hasenstaub AR

Diverse effects of stimulus history in waking mouse auditory cortex.

Journal of neurophysiology

Phillips EAK, Schreiner CE, Hasenstaub AR

Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment.

Journal of neurophysiology

Larimer P, Spatazza J, Stryker MP, Alvarez-Buylla A, Hasenstaub AR

Caudal Ganglionic Eminence Precursor Transplants Disperse and Integrate as Lineage-Specific Interneurons but Do Not Induce Cortical Plasticity.

Cell reports

Larimer P, Spatazza J, Espinosa JS, Tang Y, Kaneko M, Hasenstaub AR, Stryker MP, Alvarez-Buylla A

Inhibitory Actions Unified by Network Integration.

Neuron

Seybold BA, Phillips EAK, Schreiner CE, Hasenstaub AR

Strategies for optical control and simultaneous electrical readout of extended cortical circuits.

Journal of neuroscience methods

Ledochowitsch P, Yazdan-Shahmorad A, Bouchard KE, Diaz-Botia C, Hanson TL, He JW, Seybold BA, Olivero E, Phillips EA, Blanche TJ, Schreiner CE, Hasenstaub A, Chang EF, Sabes PN, Maharbiz MM

Cell Type-Specific Control of Spike Timing by Gamma-Band Oscillatory Inhibition.

Cerebral cortex (New York, N.Y. : 1991)

Hasenstaub A, Otte S, Callaway E

Contrast dependence and differential contributions from somatostatin- and parvalbumin-expressing neurons to spatial integration in mouse V1.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Nienborg H, Hasenstaub A, Nauhaus I, Taniguchi H, Huang ZJ, Callaway EM

Metabolic cost as a unifying principle governing neuronal biophysics.

Proceedings of the National Academy of Sciences of the United States of America

Hasenstaub A, Otte S, Callaway E, Sejnowski TJ

Cell type-specific control of neuronal responsiveness by gamma-band oscillatory inhibition.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Otte S, Hasenstaub A, Callaway EM

State changes rapidly modulate cortical neuronal responsiveness.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Hasenstaub A, Sachdev RN, McCormick DA

Enhancement of visual responsiveness by spontaneous local network activity in vivo.

Journal of neurophysiology

Haider B, Duque A, Hasenstaub AR, Yu Y, McCormick DA

Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Haider B, Duque A, Hasenstaub AR, McCormick DA

Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks.

Neuron

Hasenstaub A, Shu Y, Haider B, Kraushaar U, Duque A, McCormick DA

Barrages of synaptic activity control the gain and sensitivity of cortical neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Shu Y, Hasenstaub A, Badoual M, Bal T, McCormick DA

Persistent cortical activity: mechanisms of generation and effects on neuronal excitability.

Cerebral cortex (New York, N.Y. : 1991)

McCormick DA, Shu Y, Hasenstaub A, Sanchez-Vives M, Badoual M, Bal T

Turning on and off recurrent balanced cortical activity.

Nature

Shu Y, Hasenstaub A, McCormick DA

Brains, maturation times, and parenting.

Neurobiology of aging

Allman J, Hasenstaub A

Parenting and survival in anthropoid primates: caretakers live longer.

Proceedings of the National Academy of Sciences of the United States of America

Allman J, Rosin A, Kumar R, Hasenstaub A