Oscillatory coupling within neonatal prefrontal-hippocampal networks is independent of selective removal of GABAergic neurons in the hippocampus

- Pups with less CA1 GABAergic neurons show normal somatic development and reflexes.
- Selective lesion of CA1 GABAergic neurons impairs hippocampal sharp waves.
- Lesion of CA1 GABAergic neurons does not affect neonatal prefrontal activity.
- Prefrontal-hippocampal synchrony is similar after loss of GABAergic neurons.

GABAergic neurons have been proposed to control oscillatory entrainment and cognitive processing in prefrontal-hippocampal networks. Co-activation of these networks emerges already during neonatal development, with hippocampal theta bursts driving prefrontal oscillations via axonal projections. The cellular substrate of neonatal prefrontal-hippocampal communication and in particular, the role of GABAergic neurons, is still unknown. Here, we used saporin-conjugated anti-vesicular GABA transporter antibodies to cause selective immunotoxic lesion of GABAergic neurons in the CA1 area of the hippocampus during the first postnatal week. Without affecting the somatic development of rat pups, the lesion impaired the generation of hippocampal sharp waves, but not of theta bursts during neonatal development. Moreover, the oscillatory entrainment and firing of neonatal prefrontal cortex as well as the early prefrontal-hippocampal synchrony were largely independent of GABAergic neurotransmission in the hippocampus. Thus, hippocampal interneurons are critical elements for the ontogeny of hippocampal sharp waves, but seem to not control the directed oscillatory coupling between the neonatal prefrontal cortex and hippocampus.