About

Alfredo Kirkwood is a researcher affiliated with the Zanvyl Krieger Mind/Brain Institute at Johns Hopkins University. His work focuses on understanding neural mechanisms underlying visual processing, brain network exploration, and synaptic plasticity. His research includes studying the effects of transcranial low-intensity focused ultrasound stimulation on the visual thalamus and its long-term impact on thalamocortical synapses, as well as investigating object representation in gravitational reference frames and plasticity in models of Alzheimer’s disease and aging. Kirkwood's contributions extend to examining the neural correlates of cognitive control, decision making, and the modulation of visual cortical responses by neuromodulators such as norepinephrine and serotonin. His research aims to elucidate the complex neural processes involved in perception, cognition, and neuroplasticity.

Research topics

• Artificial Intelligence
• Computer Science
• Neuroscience
• Biology
• Physics
• Cognitive psychology
• Psychology
• Genetics

Selected publications

• NPTX2 transfection improves synaptic E/I balance and performance in learning impaired aged rats

  Progress in Neurobiology · 2025-03-07 · 3 citations

  articleSenior authorCorresponding
  PublisherDOI

• Cognitive Resilience in Aging Degus is Linked to CA3 Hippocampal GABAergic Integrity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-19

  preprint

  Abstract The preservation of cognitive function during aging remains a key challenge in neuroscience. In this study, we applied an integrative approach, combining behavioral assays with neurophysiological recordings, to investigate hippocampal circuit integrity. We used Octodon degus , a rodent with exceptional longevity (up to 10 years in laboratory conditions), as a natural model of aging and neurodegenerative disease such as Alzheimer. To assess agerelated cognitive changes, we employed three behavioral tasks: Novel Object Recognition (NOR), Open Field (OF), and the Burrowing Test (BT). The BT reflects Activities of Daily Living (ADLs) and is based on species-typical spontaneous burrowing behavior, which has been linked to neurodegenerative markers in degus. We also performed multielectrode electro-physiological recordings to assess GABAergic function in the hippocampus. Aged degus with high BT performance (classified as good burrowers, or GB) showed robust hippocampal activity, especially in the CA3 region, a key hub for signal integration and memory encoding. In contrast, degus with poor BT performance (bad burrowers, or BB) exhibited reduced spontaneous hippocampal activity, suggesting potential compensation via GABA-independent synaptic mechanisms. Altogether, our findings suggest that preserved GABAergic function supports cognitive resilience in aging degus. These results offer new insights into the neural mechanisms underlying healthy cognitive aging and may inform future strategies for preventing or mitigating neurodegeneration.

  PublisherDOI

• Eligibility traces as a synaptic substrate for learning

  Current Opinion in Neurobiology · 2025-02-16 · 9 citations

  reviewSenior author
  PublisherDOI

• Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

  iScience · 2025-02-01 · 2 citations

  erratumOpen accessSenior author

  [This corrects the article DOI: 10.1016/j.isci.2024.111494.].

  PublisherDOI

• Parallel circadian-like oscillations in LTP and excitation inhibition balance in mouse CA1 reverse direction after puberty

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-15 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Long-term potentiation (LTP), the best-characterized form of Hebbian synaptic plasticity, is well known to be under strong circadian regulation. In mice and rats, both nocturnal species, most studies indicate that LTP in the hippocampal CA1 region is more robust when induced during the dark phase. Our examination of the underlying mechanisms at the CA3 to CA1 synapse provides evidence that the capacity to express LTP does not differ between the light and dark cycles of the 24-hour day. Instead, the magnitude of theta-burst stimulation-induced LTP (TBS-LTP) correlates with daily fluctuations in the ratio of synaptic excitation to inhibition (E/I ratio): both the E/I ratio and TBS-LTP are higher during the dark phase. Consistent with a causal relationship, blockade of inhibition abolishes the light-dark difference in TBS-LTP induction, likewise, pairing-induced LTP, which is less constrained by inhibitory recruitment, does not differ between cycles. Supporting this model, using the APP/PS1 model of AD we observed that neither the E/I ratio nor TBS-LTP change during the light cycle. Finally, we made the intriguing observation that these daily oscillations reverse direction after puberty in WT mice, shifting from being larger in the dark cycle of 2-month-old mice to being larger in the light cycle in 8-month-old mice. This developmental switch may reflect an age-dependent reorganization of circadian control over hippocampal plasticity.

  PublisherOA PDFDOI

• SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity

  Science · 2024 · 80 citations

  • Neuroscience
  • Biology
  • Genetics

  -related neurodevelopmental disorders.

  PublisherOA PDFDOI

• Editorial: Insights in synaptic neuroscience 2022

  Frontiers in Synaptic Neuroscience · 2024-06-10

  editorialOpen access

  EDITORIAL article Front. Synaptic Neurosci., 10 June 2024 Volume 16 - 2024 | https://doi.org/10.3389/fnsyn.2024.1432259

  PublisherOA PDFDOI

• Daily oscillations of neuronal membrane capacitance

  Cell Reports · 2024-09-17 · 14 citations

  articleOpen access

  Capacitance of biological membranes is determined by the properties of the lipid portion of the membrane as well as the morphological features of a cell. In neurons, membrane capacitance is a determining factor of synaptic integration, action potential propagation speed, and firing frequency due to its direct effect on the membrane time constant. Besides slow changes associated with increased morphological complexity during postnatal maturation, neuronal membrane capacitance is considered a stable, non-regulated, and constant magnitude. Here we report that, in two excitatory neuronal cell types, pyramidal cells of the mouse primary visual cortex and granule cells of the hippocampus, the membrane capacitance significantly changes between the start and the end of a daily light-dark cycle. The changes are large, nearly 2-fold in magnitude in pyramidal cells, but are not observed in cortical parvalbumin-expressing inhibitory interneurons. Consistent with daily capacitance fluctuations, the time window for synaptic integration also changes in pyramidal cells.

  PublisherDOI

• Transcranial Low-Intensity Focused Ultrasound Stimulation of the Visual Thalamus Produces Long-Term Depression of Thalamocortical Synapses in the Adult Visual Cortex

  Journal of Neuroscience · 2024-02-05 · 16 citations

  articleOpen access

  Transcranial focused ultrasound stimulation (tFUS) is a noninvasive neuromodulation technique, which can penetrate deeper and modulate neural activity with a greater spatial resolution (on the order of millimeters) than currently available noninvasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). While there are several studies demonstrating the ability of tFUS to modulate neuronal activity, it is unclear whether it can be used for producing long-term plasticity as needed to modify circuit function, especially in adult brain circuits with limited plasticity such as the thalamocortical synapses. Here we demonstrate that transcranial low-intensity focused ultrasound (LIFU) stimulation of the visual thalamus (dorsal lateral geniculate nucleus, dLGN), a deep brain structure, leads to NMDA receptor (NMDAR)-dependent long-term depression of its synaptic transmission onto layer 4 neurons in the primary visual cortex (V1) of adult mice of both sexes. This change is not accompanied by large increases in neuronal activity, as visualized using the cFos Targeted Recombination in Active Populations (cFosTRAP2) mouse line, or activation of microglia, which was assessed with IBA-1 staining. Using a model (SONIC) based on the neuronal intramembrane cavitation excitation (NICE) theory of ultrasound neuromodulation, we find that the predicted activity pattern of dLGN neurons upon sonication is state-dependent with a range of activity that falls within the parameter space conducive for inducing long-term synaptic depression. Our results suggest that noninvasive transcranial LIFU stimulation has a potential for recovering long-term plasticity of thalamocortical synapses in the postcritical period adult brain.

  PublisherOA PDFDOI

• Prolonged visual deprivation in adults induces non-homeostatic plasticity of feed-forward excitation from visual thalamus to cortex

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-06

  preprintOpen access

  Age constrains plasticity at inputs from first order thalamic nuclei to the cortex, endowing stability to ascending, feed-forward projections. However, here we show that prolonged visual deprivation can induce robust and reversible plasticity at thalamocortical synapses in layer 4 pyramidal neurons in the adult mouse primary visual cortex. The plasticity engaged by prolonged visual deprivation is non-homeostatic and mediated by changes in presynaptic function.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R03TW007171

  NIH · $117k · 2010

• PROJECT 1-Neural encoding based on lateral and medial entorhinal information processing streams in behaviorally-characterized aged rats

  NIH · $72.5M · 1997–2027

• Regulation of Synaptic Plasticity in Visual Cortex

  NIH · $8.0M · 1998–2023

• NIH Grant R01AG034606

  NIH · $1.9M · 2015

• Reversible activation of critical period plasticity in visual cortex

  NIH · $3.6M · 2015–2025

Frequent coauthors

• Hey‐Kyoung Lee

  Johns Hopkins University

  55 shared

• Daniel Severín

  Johns Hopkins University

  48 shared

• Mark F. Bear

  Massachusetts Institute of Technology

  44 shared

• Michelle Bridi

  West Virginia University

  38 shared

• Shiyong Huang

  Hubei University of Arts and Science

  29 shared

• Trinh Tran

  National Institutes of Health

  26 shared

• Richard L. Huganir

  Johns Hopkins Medicine

  25 shared

• Bernardo Morales

  Universidad de Santiago de Chile

  23 shared

Labs

• Collaborative studies across MBI labsPI