Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.

Synaptophysin immunoreactivity in the human hippocampus and neocortex from 6 to 41 weeks of gestation.

To assess the synaptic vesicle protein synaptophysin as a potential marker for maturation in the human fetal brain, synaptophysin immunoreactivity (sIR) was prospectively studied in postmortem sections of 162 normal human fetal and neonatal brains of both sexes from 6 to 41 weeks' gestational age. There was a consistent temporal and spatial pattern of sIR in the hippocampus and cerebral neocortex. In the rostral hippocampus, sIR was first apparent in the molecular zone of the dentate gyrus at 12 weeks, followed by CA2 at 14 weeks, CA3 and CA4 at 15 to 16 weeks, and CA1 at 19 weeks; it was incomplete until 26 weeks. In frontal neocortex, sIR developed in a laminar pattern above and below the cortical plate as early as 12 weeks, around Cajal-Retzius neurons of the molecular zone at 14 weeks, surrounding pyramidal neurons of Layers 5 and 6 at 16 weeks, and at the surface of neuronal somata in Layers 2 and 4 at 22 weeks. At 33 weeks, Layers 2 and 4 still had less sIR than other layers. Uniform sIR among all cortical layers was evident at 38 weeks. Ascending probable thalamocortical axons were reactive as early as 12 weeks and were best demonstrated by 26 weeks, after which increasing sIR in the neuropil diminished the contrast. The sIR was preserved for more than 96 hours postmortem, even in severely autolytic brains. We conclude that synaptophysin is a reliable marker in human fetal brain and that sIR provides the means for objective assessment of cerebral maturation in normal brains and to enable interpretation of abnormal synaptic patterns in pathological conditions.