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Updated: Sep 22, 2025

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
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Adolescent thalamic inhibition leads to long-lasting impairments in prefrontal cortex function

Laura J Benoit1, Emma S Holt2,3, Lorenzo Posani4,5

  • 1Graduate Program in Neurobiology and Behavior, Columbia University Irving Medical Center, New York, NY, USA.

Nature Neuroscience
|May 19, 2022
PubMed

Insights

Adolescent thalamic activity is crucial for prefrontal cortex development and cognitive function. Boosting thalamic activity in adulthood can rescue cognitive deficits linked to neurodevelopmental disorders.

Area of Science:

  • Neuroscience
  • Developmental Neuroscience
  • Cognitive Neuroscience

Background:

  • Impaired cortical maturation is implicated in neurodevelopmental disorders like schizophrenia.
  • Thalamic input during postnatal periods is vital for sensory cortex development.
  • The role of thalamic activity in prefrontal cortex maturation remains unclear.

Purpose of the Study:

  • To investigate the impact of thalamic activity on prefrontal cortex maturation during adolescence.
  • To determine if thalamic input shapes prefrontal cortical development and cognitive functions.
  • To explore potential therapeutic strategies targeting thalamocortical circuits.

Main Methods:

  • Inhibition of the mediodorsal and midline thalamus in adolescent mice.
  • Assessment of thalamo-prefrontal projection density and neuronal excitatory drive.
  • Evaluation of prefrontal-dependent cognitive behaviors in adulthood.
  • Electrophysiological recordings to analyze prefrontal network activity.

Main Results:

  • Adolescent thalamic inhibition caused lasting reductions in thalamo-prefrontal projections and excitatory drive.
  • Cognitive deficits and disrupted prefrontal network activity were observed in adulthood following adolescent inhibition.
  • Adult thalamic inhibition had no long-term effects, while adult thalamic stimulation rescued cognitive deficits.

Conclusions:

  • Adolescence represents a sensitive period for thalamocortical circuit maturation, particularly for the prefrontal cortex.
  • Thalamic input during adolescence is essential for establishing normal prefrontal cortical function and cognitive abilities.
  • Enhancing thalamic activity may offer a therapeutic approach for neurodevelopmental disorders characterized by cognitive impairments.

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