Peter Koppensteiner1, Richard Von Itter1, Riccardo Melani1, Christopher Galvin1, Francis S Lee2, Ipe Ninan3. 1. Department of Psychiatry, NYU Langone Medical Center, New York, New York. 2. Department of Psychiatry, Weill Cornell Medicine, New York, New York. 3. Department of Psychiatry, NYU Langone Medical Center, New York, New York; NYU Neuroscience Institute, NYU Langone Medical Center, New York, New York. Electronic address: ipe.ninan@nyulangone.org.
Abstract
BACKGROUND: Rodents and humans show an attenuation of fear extinction during adolescence, which coincides with the onset of several psychiatric disorders. Although the ethological relevance and the underlying mechanism are largely unknown, the suppression of fear extinction during adolescence is associated with a diminished plasticity in the glutamatergic neurons of the infralimbic medial prefrontal cortex, a brain region critical for fear extinction. Given the putative effect of synaptic inhibition on glutamatergic neuron activity, we studied whether gamma-aminobutyric acidergic neurons in the infralimbic medial prefrontal cortex are involved in the suppression of fear extinction during adolescence. METHODS: We assessed membrane and synaptic properties in parvalbumin-positive interneurons (PVINs) and somatostatin-positive interneurons (SSTINs) in male preadolescent, adolescent, and adult mice. The effect of fear conditioning and extinction on PVIN-pyramidal neuron and SSTIN-pyramidal neuron synapses in male preadolescent, adolescent, and adult mice was evaluated using an optogenetic approach. RESULTS: The development of the membrane excitability of PVINs is delayed and reaches maturity only by adulthood, while the SSTIN membrane properties are developed early and remain stable during development from preadolescence to adulthood. Although the synaptic inhibition mediated by PVINs undergoes a protracted development, it does not exhibit a fear behavior-specific plasticity. However, the synaptic inhibition mediated by SSTINs undergoes an adolescence-specific enhancement, and this increased inhibition is suppressed by fear learning but is not restored by extinction training. This altered plasticity during adolescence overlapped with a reduction in calcium-permeable glutamate receptors in SSTINs. CONCLUSIONS: The adolescence-specific plasticity in the SSTINs might play a role in fear extinction suppression during adolescence in mice.
BACKGROUND: Rodents and humans show an attenuation of fear extinction during adolescence, which coincides with the onset of several psychiatric disorders. Although the ethological relevance and the underlying mechanism are largely unknown, the suppression of fear extinction during adolescence is associated with a diminished plasticity in the glutamatergic neurons of the infralimbic medial prefrontal cortex, a brain region critical for fear extinction. Given the putative effect of synaptic inhibition on glutamatergic neuron activity, we studied whether gamma-aminobutyric acidergic neurons in the infralimbic medial prefrontal cortex are involved in the suppression of fear extinction during adolescence. METHODS: We assessed membrane and synaptic properties in parvalbumin-positive interneurons (PVINs) and somatostatin-positive interneurons (SSTINs) in male preadolescent, adolescent, and adult mice. The effect of fear conditioning and extinction on PVIN-pyramidal neuron and SSTIN-pyramidal neuron synapses in male preadolescent, adolescent, and adult mice was evaluated using an optogenetic approach. RESULTS: The development of the membrane excitability of PVINs is delayed and reaches maturity only by adulthood, while the SSTIN membrane properties are developed early and remain stable during development from preadolescence to adulthood. Although the synaptic inhibition mediated by PVINs undergoes a protracted development, it does not exhibit a fear behavior-specific plasticity. However, the synaptic inhibition mediated by SSTINs undergoes an adolescence-specific enhancement, and this increased inhibition is suppressed by fear learning but is not restored by extinction training. This altered plasticity during adolescence overlapped with a reduction in calcium-permeable glutamate receptors in SSTINs. CONCLUSIONS: The adolescence-specific plasticity in the SSTINs might play a role in fear extinction suppression during adolescence in mice.
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