About

Professor Alison Barth is a Principal Investigator at the Barth Lab. She holds a Ph.D. from the University of California, Berkeley, and completed a postdoctoral appointment at Stanford University School of Medicine. Her research focuses on understanding neural mechanisms, as indicated by her role as a principal investigator in a neuroscience-related lab. The page provides no further specific details about her research contributions, publications, or areas of specialization.

Research topics

• Computer Science
• Artificial Intelligence
• Neuroscience
• Psychology
• Materials science
• Biology
• Optics
• Medicine
• Optoelectronics
• Cognitive psychology
• Biophysics
• Biomedical engineering
• Nanotechnology
• Audiology
• Engineering

Selected publications

• Sexually dimorphic plasticity of PV inhibition in sensory neocortex during learning

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-12

  articleOpen accessSenior authorCorresponding

  Abstract Neocortical parvalbumin-expressing (PV) neurons critically regulate circuit excitation by strong synaptic inputs onto local pyramidal (Pyr) neurons. Plasticity in PV-mediated inhibition during learning could have pronounced effects on gating excitatory synaptic plasticity and circuit excitability, but experimental evidence to support this input- and target-specific plasticity is scant. Here, we combined in vitro electrophysiology with quantitative synapse analysis to determine whether training in a whisker-based sensory-association task could alter PV-mediated inhibition in the primary somatosensory cortex of mice. Using light-evoked activation of channelrhodopsin-expressing PV neurons, we found that evoked PV-IPSCs in Pyr neurons from layer (L) 2/3, but not L5, were rapidly suppressed at the onset of training. This reduction was sex-specific, occurring only in females. The training-related decrease in PV output was accompanied by a reduced number of PV-associated synapses on both the soma and dendrites of L2/3 Pyr neurons, suggesting a postsynaptic structural change. Notably, when whisker stimulation was decoupled from the water reward during pseudotraining, PV-mediated inhibition remained stable. Thus, reduced PV inhibition in superficial layers is an early response to the development of stimulus-reward associations during sensory learning. In addition, these data underscore the importance of including sex as a biological variable in studies of learning-related cortical plasticity.

  PublisherOA PDFDOI

• Ih Shapes Pathway-Specific Inhibition in Substantia Nigra Pars Reticulata

  Journal of Neuroscience · 2026-05-07

  article

  The substantia nigra pars reticulata (SNr) functions as the principal inhibitory output of the basal ganglia, with the timing of its spikes critically controlling downstream disinhibition required for movement initiation. The external globus pallidus (GPe) and D1-expressing medium spiny neurons (D1-MSNs) in the striatum provide GABAergic inputs to the SNr that differ in their amplitude and kinetic properties. How these inputs interact with the intrinsic membrane currents that determine SNr firing is only partially understood. Using optogenetics, computational modeling, and electrophysiology in acute mouse brain slices, 47 animals of either sex were used for measurements, and we found an unexpected interaction between GABAergic inputs and hyperpolarization-activated currents (Ih) that tunes inhibitory efficacy in a pathway-specific manner. GPe inputs evoke fast, large IPSCs that transiently suppress SNr firing within a narrow window but whose rapid decay enables depolarization from Ih to restore firing after only a brief pause. In contrast, the slower decay kinetics of striatal IPSCs enables more sustained inhibition that counters the depolarizing drive from Ih to produce longer pauses, despite their lower conductance amplitudes. Pharmacological blockade of Ih with ZD7288 eliminated the rapid recovery of firing after GPe inhibition and equalized the inhibitory efficacy between GPe and striatal pathways. These findings establish an important interplay between synaptic kinetics and intrinsic membrane conductances in establishing pathway-specific inhibitory balance in the basal ganglia. Significant statement Our study reveals that inhibitory pathways to the substantia nigra pars reticulata are differentially shaped by the interplay between synaptic kinetics and intrinsic membrane conductances. Using optogenetics, electrophysiology, and modeling, we showed that fast-decaying GABAergic inputs from the external globus pallidus are rapidly overcome by Ih, producing only brief pauses in SNr firing, whereas slower striatal inputs generate longer-lasting inhibition. Blocking Ih abolishes this difference, demonstrating that intrinsic currents tune inhibitory efficacy in a pathway-specific manner. These results identify a biophysical mechanism that helps set the balance of basal ganglia output essential for movement control.

  PublisherDOI

• Sexually dimorphic plasticity of PV inhibition in sensory neocortex during learning

  Scientific Reports · 2026-01-10

  articleOpen accessSenior author

  Neocortical parvalbumin-expressing (PV) neurons critically regulate circuit excitation by strong synaptic inputs onto local pyramidal (Pyr) neurons. Plasticity in PV-mediated inhibition during learning could have pronounced effects on gating excitatory synaptic plasticity and circuit excitability, but experimental evidence to support this input- and target-specific plasticity is scant. Here, we used in vitro electrophysiology to determine whether training in a whisker-based sensory-association task could alter PV-mediated inhibition in the primary somatosensory cortex of mice. Using light-evoked activation of channelrhodopsin-expressing PV neurons, we found that evoked PV-IPSCs in Pyr neurons from layer (L) 2/3, but not L5, were rapidly suppressed at the onset of training. This reduction was sex-specific, occurring only in females. Notably, when whisker stimulation was decoupled from the water reward during pseudotraining, PV-mediated inhibition remained stable. Thus, reduced PV inhibition in superficial layers is an early response to the development of stimulus-reward associations during sensory learning. In addition, these data underscore the importance of including sex as a biological variable in studies of learning-related cortical plasticity.

  PublisherOA PDFDOI

• Learning, prediction accuracy, and neural plasticity in sensory cortex

  Current Opinion in Neurobiology · 2025-07-15 · 2 citations

  reviewOpen access1st authorCorresponding

  Causal inference during association learning is a cardinal feature of complex nervous systems. In reinforcement learning, a stimulus or context becomes linked to a negative or positive outcome to inform future behavior. Although prefrontal cortex and striatal circuits have been implicated in reinforcement learning, sensory cortex also undergoes marked short-term and long-lasting changes. Here we review studies demonstrating anatomical, synaptic, and task-dependent response plasticity in sensory cortex during learning. A contrast between plasticity induced by sensory association learning, where stimuli predict reinforcement outcomes, and pseudotraining, where sensory inputs are uncoupled, is consistent with sensory cortex's role in prediction evaluation and reinforcement signaling. We propose that plasticity in sensory cortex–a site for collision of internally-generated expectations and incoming sensory input–reflects the relative accuracy of expected versus actual sensory signals as they develop during learning. Sensory learning may thus be a useful tool to probe the function of neocortical circuits. • Associative learning extensively modifies sensory neocortex. • Diverse training protocols influence specific cellular targets and pathways. • Learning alters both higher-order and intracortical inputs. • Stimulus-reinforcement contingencies bidirectionally modulate SST responses. • Neuromodulators convey uncertainty and associative learning signals.

  PublisherDOI

• Neocortical somatostatin neuron diversity in cognition and learning

  Trends in Neurosciences · 2025-01-16 · 15 citations

  reviewOpen accessSenior author

  Somatostatin-expressing (SST) neurons are a major class of electrophysiologically and morphologically distinct inhibitory cells in the mammalian neocortex. Transcriptomic data suggest that this class can be divided into multiple subtypes that are correlated with morpho-electric properties. At the same time, availability of transgenic tools to identify and record from SST neurons in awake, behaving mice has stimulated insights about their response properties and computational function. Neocortical SST neurons are regulated by sleep and arousal, attention, and novelty detection, and show marked response plasticity during learning. Recent studies suggest that subtype-specific analysis of SST neurons may be critical for understanding their complex roles in cortical function. In this review, we discuss and synthesize recent advances in understanding the diversity, circuit integration, and functional properties of this important group of GABAergic neurons.

  PublisherDOI

• Somatostatin neurons detect stimulus-reward contingencies to reduce neocortical inhibition during learning

  Cell Reports · 2025-04-20 · 6 citations

  articleOpen accessSenior author

  Learning involves the association of discrete events in the world to infer causality, likely through a cascade of changes at input- and target-specific synapses. Transient or sustained disinhibition may initiate cortical circuit plasticity important for association learning, but the cellular networks involved have not been well defined. Using recordings in acute brain slices, we show that whisker-dependent sensory association learning drives a durable, target-specific reduction in inhibition from somatostatin (SST)-expressing GABAergic neurons onto pyramidal (Pyr) neurons in superficial but not deep layers of mouse somatosensory cortex. Critically, SST output was not altered when stimuli and rewards were unpaired, indicating that these neurons are sensitive to stimulus-reward contingency. Depression of SST output onto Pyr neurons could be phenocopied by chemogenetic suppression of SST activity outside of the training context. Thus, neocortical SST neuron output can undergo long-lasting modifications to selectively disinhibit superficial layers of sensory neocortex during learning.

  PublisherDOI

• Long-lasting, subtype-specific regulation of somatostatin interneurons during sensory learning

  Science Advances · 2025-08-15 · 4 citations

  articleOpen accessSenior authorCorresponding

  Somatostatin (SST)-expressing inhibitory neurons are a major class of neocortical γ-aminobutyric acid neurons, where morphological, electrophysiological, and transcriptomic analyses indicate more than a dozen different subtypes. However, whether this diversity is related to specific roles in cortical computations and plasticity remains unclear. Here, we identify learning-dependent, subtype-specific plasticity in layer 2/3 SST neurons of the mouse somatosensory cortex. Martinotti-type, SST neurons expressing calbindin-2 show a selective decrease in excitatory synaptic input and stimulus-evoked calcium responses, as mice learn a stimulus-reward association. Using these insights, we develop a label-free classifier using basal activity from in vivo imaging that accurately predicts learning-associated response plasticity. Our data indicate that molecularly defined SST neuron subtypes play specific and highly regulated roles in sensory information processing and learning.

  PublisherDOI

• A brief history of somatostatin interneuron taxonomy or: how many somatostatin subtypes are there, really?

  Frontiers in Neural Circuits · 2024-07-17 · 14 citations

  reviewOpen accessSenior author

  We provide a brief (and unabashedly biased) overview of the pre-transcriptomic history of somatostatin interneuron taxonomy, followed by a chronological summary of the large-scale, NIH-supported effort over the last ten years to generate a comprehensive, single-cell RNA-seq-based taxonomy of cortical neurons. Focusing on somatostatin interneurons, we present the perspective of experimental neuroscientists trying to incorporate the new classification schemes into their own research while struggling to keep up with the ever-increasing number of proposed cell types, which seems to double every two years. We suggest that for experimental analysis, the most useful taxonomic level is the subdivision of somatostatin interneurons into ten or so "supertypes," which closely agrees with their more traditional classification by morphological, electrophysiological and neurochemical features. We argue that finer subdivisions ("t-types" or "clusters"), based on slight variations in gene expression profiles but lacking clear phenotypic differences, are less useful to researchers and may actually defeat the purpose of classifying neurons to begin with. We end by stressing the need for generating novel tools (mouse lines, viral vectors) for genetically targeting distinct supertypes for expression of fluorescent reporters, calcium sensors and excitatory or inhibitory opsins, allowing neuroscientists to chart the input and output synaptic connections of each proposed subtype, reveal the position they occupy in the cortical network and examine experimentally their roles in sensorimotor behaviors and cognitive brain functions.

  PublisherOA PDFDOI

• Transient enhancement of stimulus-evoked activity in neocortex during sensory learning

  Learning & Memory · 2024-06-01 · 14 citations

  articleOpen accessSenior author

  imaging in the barrel cortex of awake mice to test the hypothesis that increased excitatory synaptic strength during the learning of a whisker-dependent sensory-association task would be correlated with enhanced stimulus-evoked firing. To isolate stimulus-evoked responses from dynamic, task-related activity, imaging was performed outside of the training context. Although prior studies indicate that multiwhisker stimuli drive robust subthreshold activity, we observed sparse activation of L2/3 pyramidal (Pyr) neurons in both control and trained mice. Despite evidence for excitatory synaptic strengthening at thalamocortical and intracortical synapses in this brain area at the onset of learning-indeed, under our imaging conditions thalamocortical axons were robustly activated-we observed that L2/3 Pyr neurons in somatosensory (barrel) cortex displayed only modest increases in stimulus-evoked activity that were concentrated at the onset of training. Activity renormalized over longer training periods. In contrast, when stimuli and rewards were uncoupled in a pseudotraining paradigm, stimulus-evoked activity in L2/3 Pyr neurons was significantly suppressed. These findings indicate that sensory-association training but not sensory stimulation without coupled rewards may briefly enhance sensory-evoked activity, a phenomenon that might help link sensory input to behavioral outcomes at the onset of learning.

  PublisherDOI

• Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis

  iScience · 2024-08-02 · 12 citations

  articleOpen accessSenior author

  The limited success of plaque-reducing therapies in Alzheimer's disease suggests that early treatment might be more effective in delaying or reversing memory impairments. Toward this end, it is important to establish the progression of synaptic and circuit changes before onset of plaques or cognitive deficits. Here, we used quantitative, fluorescence-based methods for synapse detection in CA1 pyramidal neurons to investigate the interaction between abnormal circuit activity, measured by Fos-immunoreactivity, and synapse reorganization in mouse models of amyloidosis. Using a genetically encoded, fluorescently labeled synaptic marker in juvenile mice (prior to sexual maturity), we find both synapse gain and loss depending on dendritic location. This progresses to broad synapse loss in aged mice. Elevated hippocampal activity in both CA3 and CA1 was present at weaning and preceded this reorganization. Thus, Aβ overproduction may initiate abnormal activity and subsequent input-specific synapse plasticity. These findings indicate that sustained amyloidosis drives heterogeneous and progressive circuit-wide abnormalities.

  PublisherDOI

Recent grants

• Synaptic plasticity in sensory learning

  NIH · $397k · 2022–2025

• High Throughput Approaches for Cell-Specific Synapse Characterization

  NIH · $299k · 2017–2021

• High Throughput Approaches for Cell-Specific Synapse Characterization

  NIH · $2.2M · 2017–2021

• Determinants of sparse activity in neocortex

  NIH · $2.5M · 2022–2026

• NIH Grant R21MH100612

  NIH · $420k · 2016

Frequent coauthors

• Joanna Urban-Ciećko

  Instytut Biologii Doświadczalnej im. Marcelego Nenckiego

  38 shared

• Marcel P. Bruchez

  Carnegie Mellon University

  23 shared

• Brett L. Benedetti

  20 shared

• Christopher P. Pratt

  Northwestern University

  16 shared

• James F.A. Poulet

  Max Delbrück Center

  16 shared

• Jing Wen

  16 shared

• Jianjun He

  Hunan University

  14 shared

• Nicholas J. Audette

  New York University

  13 shared

Labs

• Barth LabPI

Education

• Ph.D.

  University of California, Berkeley

• Other

  Stanford University School of Medicine

Awards & honors

• Maxwell H. and Gloria C. Connan Professor in the Life Scienc…