Excitatory postsynaptic potential

Neuroscience

Pyramidal cell

Interneuron

Cerebral cortex

Biology

Inhibitory postsynaptic potential

Hippocampus

Nature

Complex neuronal circuitries such as those found in the mammalian cerebral cortex have evolved as balanced networks of excitatory and inhibitory neurons. Although the establishment of appropriate numbers of these cells is essential for brain function and behaviour, our understanding of this fundamental process is limited. Here we show that the survival of interneurons in mice depends on the activity of pyramidal cells in a critical window of postnatal development, during which excitatory synaptic input to individual interneurons predicts their survival or death. Pyramidal cells regulate interneuron survival through the negative modulation of PTEN signalling, which effectively drives interneuron cell death during this period. Our findings indicate that activity-dependent mechanisms dynamically adjust the number of inhibitory cells in nascent local cortical circuits, ultimately establishing the appropriate proportions of excitatory and inhibitory neurons in the cerebral cortex. Excitatory input onto inhibitory interneurons in the developing mouse cortex acts through PTEN to protect interneurons from cell death and thus regulate the balance between excitation and inhibition.

Pyramidal cell regulation of interneuron survival sculpts cortical networks