# Effects of adolescent synaptic pruning on cortical signal processing

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $366,419

## Abstract

Project Summary
Postmortem studies indicate that synaptic pruning continues through adolescence into adulthood in prefrontal
cortex (PFC) at time when cognitive abilities optimize and major psychopathologies (e.g., schizophrenia, mood
disorders, substance use disorders) emerge. However, understanding this process in vivo and its effects on
maturation of neurocognitive function is not well understood. The recently funded parent R01 proposes a suite
of MR-based acquisitions to assess synaptic pruning in vivo using ultra high field (7 Tesla) 31P MRI, diffusion
weighted imaging (DWI) and MR spectroscopic imaging (MRSI). This competing supplement aims to extend this
work in two aims. First, we will add critical direct characterizations of synaptic pruning from a subset of adult
participants from the parent grant using the tracer [11C]UCB-J which has been well validated as the gold
standard in vivo measure of synapse density. Regional and whole-brain analyses will characterize the
relationship between MR and PET-based measures of synaptic density to demonstrate how MRI can be used to
assess developmental synapse reduction. Second, we will use EEG data collected from all the participants of
the parent grant to understand how PFC synaptic pruning supports neurocognitive maturation via development
of electrophysiological properties of functional brain activity. Adolescent pruning of excitatory synapses has been
proposed as a mechanism for optimizing cortical signal processing, driving the rebalancing of excitatory-
inhibitory (E/I) signaling associated with adolescent brain plasticity. Interactions among these neural signaling
systems support the development of oscillatory activity, suppression of spontaneous neural firing, and
enhancement of cortical signal-to-noise ratios, which together support the emergence of adult levels of reliable
cognitive processing. EEG data will be used to assess both periodic (oscillatory) and aperiodic (non-cyclical)
activity, to characterize how synaptic pruning reshapes these aspects of neural signal processing through
adolescence. This study will not only increase the impact of our ongoing studies, but importantly will provide a
first-ever comprehensive assessment of how reliable, accessible measurements of synaptic pruning can be used
to assess cortical signal processing. This will have a wide ranging impact in stimulating research related to
synaptic pruning across disciplines: pruning has been linked to a number of mental health and
neurodevelopmental disorders, including schizophrenia, autism, ADHD, bipolar disorder, and more. Providing
the field with validated tools to better assess these processes in vivo using accessible methodologies such as
MRI and EEG, in conjunction with the results emerging from the proposed studies characterizing adolescent
neurodevelopment, will advance our understanding of the neurophysiological mechanisms driving plasticity
through this critical period, and how disruptions to these process...

## Key facts

- **NIH application ID:** 10976573
- **Project number:** 3R01MH067924-19S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** BEATRIZ LUNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $366,419
- **Award type:** 3
- **Project period:** 2004-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10976573

## Citation

> US National Institutes of Health, RePORTER application 10976573, Effects of adolescent synaptic pruning on cortical signal processing (3R01MH067924-19S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10976573. Licensed CC0.

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