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Effect of juvenile social isolation on excitability of prefrontal pyramidal cells with different subcortical axonal
Yosuke Nishihata1, Hiroki Yoshino1,2, Yoichi Ogawa3
1Department of Psychiatry, Nara Medical University, Kashihara, Japan.
Insights
Juvenile social isolation (JSI) impacts prefrontal cortex development. JSI differentially affects layer-5 pyramidal cells based on their specific subcortical projection targets, influencing neural function.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Systems Neuroscience
Background:
- Social experience is vital for prefrontal cortex maturation.
- Juvenile social isolation (JSI) leads to prefrontal cortex dysfunction.
- JSI impairs specific layer-5 (L5) pyramidal cells in the medial prefrontal cortex.
Purpose of the Study:
- To identify subcortical projection targets of L5 pyramidal cells affected by JSI.
- To compare functional properties of L5 pyramidal cell subclasses.
- To investigate the impact of JSI on these subclasses.
Main Methods:
- Retrograde neuronal tracing to identify L5 pyramidal cell projection targets (mediodorsal thalamus, striatum, pontine nuclei).
- Electrophysiological analysis of intrinsic membrane properties and excitatory synaptic inputs.
- Assessment of JSI effects on these cellular properties.
Main Results:
- L5 pyramidal cells projecting to pontine nuclei exhibit distinct intrinsic properties and more excitatory inputs compared to those projecting to the mediodorsal thalamus or striatum.
- JSI enhances firing responsiveness in mediodorsal thalamus-projecting cells.
- JSI reduces excitatory synaptic inputs specifically in pontine nuclei-projecting cells.
Conclusions:
- The developmental effects of JSI on L5 pyramidal cells are target-specific.
- Projection target dictates vulnerability to JSI-induced alterations in neural function.
Background:
Social experience during development is crucial for the functional maturation of the prefrontal cortex (PFC). Juvenile social isolation (JSI) causes severe PFC dysfunction. JSI reduces intrinsic excitability and excitatory synaptic inputs for a subtype of layer-5 (L5) pyramidal cells showing prominent h-current (PH cells) in the medial PFC. PH cells do not have commissural or associational cortical output; instead, they project into subcortical areas. However, which subcortical area is the projection target of L5 pyramidal cells affected by JSI remains unascertained.
Methods:
Using retrograde neuronal tracing, we identified L5 pyramidal cells having three different projection targets: the mediodorsal thalamus, striatum, or pontine nuclei. We elucidated differences in functional properties among the three subclasses of L5 pyramidal cells and examined how JSI affects the intrinsic membrane properties and excitatory inputs for each class of L5 pyramidal cells.
Results:
Pyramidal cells projecting to the pontine nuclei had more excitatory synaptic inputs and more distinguishing intrinsic properties than pyramidal cells projecting to the mediodorsal thalamus and striatum. JSI increased the firing responsiveness of pyramidal cell projecting to mediodorsal thalamus and reduced excitatory synaptic inputs only onto pyramidal cells projecting to the pontine nuclei.
Conclusion:
JSI affects the development of L5 pyramidal cells based on their projection target.
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