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<p>The immune system provides multiple layers of protection that extend beyond conventional pathogen defense, including context-dependent modulation of behavior. However, the mechanisms driving these immune-mediated behavioral modifications remain incompletely understood. Here, we demonstrate that group 2 innate lymphoid cells (ILC2s) shape hippocampal synaptic development during early postnatal stages, with lasting effects on adult behavior, learning, and memory.</p><p>Using flow synaptometry, we identified a selective reduction in hippocampal VGAT<sup>+</sup> GABAergic/glycinergic inhibitory synapse frequency at postnatal day 15 in ILC2-deficient mice, while the proportions of inhibitory GABAergic (NL2<sup>+</sup>) or excitatory glutamatergic (GluR1<sup>+</sup>) synapses remained unaltered. These synaptic changes occurred without detectable phenotypical changes in cortical and hippocampal microglia. In adulthood, ILC2-deficient mice displayed significant impairments in hippocampus-dependent tasks, such as active place avoidance and operant conditioning, reflecting deficits in learning and memory.</p><p>Our findings reveal a critical role for ILC2s in the formation of inhibitory synapses in the hippocampus, highlighting the impact of immune signaling on neuronal network maturation during a crucial period of brain development. This early immune-mediated modulation may have lasting effects on neuronal circuitry and cognitive functions that persist into adulthood, emphasizing the long-term implications of neuro-immune interactions for normal cognitive development and function.</p>

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Group 2 innate lymphoid cells drive inhibitory synapse formation with lasting effects on learning and memory

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月23日

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  • Johannes Steffen,
  • Divija Deshpande,
  • Henning Peter Düsedau,
  • Janna Schmitz,
  • Caio Andreeta Figueiredo,
  • Laura Velleman,
  • Claudia Pitzer,
  • Christoph S.N. Klose,
  • Ildiko R. Dunay

摘要

The immune system provides multiple layers of protection that extend beyond conventional pathogen defense, including context-dependent modulation of behavior. However, the mechanisms driving these immune-mediated behavioral modifications remain incompletely understood. Here, we demonstrate that group 2 innate lymphoid cells (ILC2s) shape hippocampal synaptic development during early postnatal stages, with lasting effects on adult behavior, learning, and memory.

Using flow synaptometry, we identified a selective reduction in hippocampal VGAT+ GABAergic/glycinergic inhibitory synapse frequency at postnatal day 15 in ILC2-deficient mice, while the proportions of inhibitory GABAergic (NL2+) or excitatory glutamatergic (GluR1+) synapses remained unaltered. These synaptic changes occurred without detectable phenotypical changes in cortical and hippocampal microglia. In adulthood, ILC2-deficient mice displayed significant impairments in hippocampus-dependent tasks, such as active place avoidance and operant conditioning, reflecting deficits in learning and memory.

Our findings reveal a critical role for ILC2s in the formation of inhibitory synapses in the hippocampus, highlighting the impact of immune signaling on neuronal network maturation during a crucial period of brain development. This early immune-mediated modulation may have lasting effects on neuronal circuitry and cognitive functions that persist into adulthood, emphasizing the long-term implications of neuro-immune interactions for normal cognitive development and function.