Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation

Abstract

Introduction: Parvalbumin (PV) is a calcium-binding protein present in fast-spiking GABAergic neurons, such as basket and axo-axonic cells. Previous studies in non-human primates reported prenatal expression of PV in the temporal archicortex including entorhinal cortex and hippocampal formation. In contrast, PV-immunoreactivity was observed only postnatally in the human entorhinal cortex. Regarding PV expression in the human hippocampal formation, no information is available.Methods: In this study, the neurochemical maturation of PV-immunoreactive interneurons was studied in the postnatal developing human hippocampal formation.Results: Before birth, no PV-immunoreactive neurons could be detected in the human hippocampus. At birth, only a few PV-immunoreactive neurons were visible in Ammon’s horn. The first PV-immunoreactive cells in the hilus of the dentate gyrus appeared at the age of 1 month. Even at the age of 5 months, only a few PV-immunopositive cells were present in the dentate hilus. The number of cells and their dendritic and axonal arborization in Ammon’s horn and in the dentate gyrus gradually increased with age. Even at the age of 2 years, dendritic tree and axons of PV-immunoreactive neurons were less complex than can be seen in 8 and 11 years old children.Discussion: Our results showed that long-lasting maturation of PV-immunoreactive interneurons follows the developmental sequence of the subfields of the human hippocampal formation and provides further morphological evidence for the long-lasting functional maturation of the human cortex.

Postweaning development influences endogenous VPAC1 modulation of LTP induced by theta-burst stimulation: a link to maturation of the hippocampal GABAergic system?

“…Studies on the maturation of hippocampal GABAergic transmission and its relations to GABAergic synapse establishment and synaptic plasticity are more often focused on early preweaning brain development [57], but accumulated evidence suggests that maturation of hippocampal circuits continues to progress into childhood and adolescence [58]. This involves not only maturation of resting properties and the setting up of new or altered synaptic connections but also the migration and insertion of new neurons, and involved most prominently interneurons and their synaptic spines [35,58,59]. The observations in the present work are consistent with these studies.…”

“…Accumulated evidence suggests that interneurons serve as mediators of normal circuit development by regulating critical period plasticity and shaping the formation of sensory maps [33]. Furthermore, although interneurons are present in the hippocampus from early postnatal development, a few of these, like parvalbumin-expressing interneurons only fully develop and set in human hippocampal circuits until adulthood [35] This can dramatically influence the dynamics of hippocampal inhibition from weaning to adulthood, and its control of synaptic plasticity phenomena. We showed recently that TBS-induced LTP undergoes post-weaning developmental maturation until adulthood [36], and preliminary data from our lab suggests this may be related to postweaning maturation of GABAergic circuits [37].…”

Postweaning Development Influences Endogenous VPAC1 Modulation of LTP Induced by Theta-Burst Stimulation: A Link to Maturation of the Hippocampal GABAergic System

“…Studies on the maturation of hippocampal GABAergic transmission and its relations to GABAergic synapse establishment and synaptic plasticity are more often focused on early preweaning brain development [ 52 ], but accumulated evidence suggests that the maturation of hippocampal circuits continues to progress into childhood and adolescence [ 53 ]. This involves not only the maturation of resting properties and the setting up of new or altered synaptic connections but also the migration and insertion of new neurons, and involved most prominently interneurons and their synaptic spines [ 33 , 53 , 54 ]. The observations in the present work are consistent with these studies.…”

“…Accumulated evidence suggests that interneurons serve as mediators of normal circuit development by regulating critical period plasticity and shaping the formation of sensory maps [ 31 ]. Furthermore, although interneurons are present in the hippocampus from early postnatal development, a few of these, like parvalbumin-expressing interneurons only fully develop and set in human hippocampal circuits until adulthood [ 33 ] This can dramatically influence the dynamics of hippocampal inhibition from weaning to adulthood, and its control of synaptic plasticity phenomena. We showed recently that TBS-induced LTP undergoes post-weaning developmental maturation until adulthood [ 34 ], and preliminary data from our lab suggests this may be related to postweaning maturation of GABAergic circuits [ 35 ].…”

Genetic implication of prenatal GABAergic and cholinergic neuron development in susceptibility to schizophrenia

“…We 23 and others 37 have found particularly strong enrichment of schizophrenia common variant genetic risk in developing glutamatergic neurons of the prenatal brain, although those and the present findings indicate an independent contribution of GABAergic neuron development. A limitation of our study is that we were not able to test enrichment of schizophrenia genetic risk in parvalbumin-positive GABAergic interneurons, which have been strongly implicated in schizophrenia through post-mortem studies 6–8 , as parvalbumin is not expressed in these neurons until after birth 64–66 . Further insight into the cellular etiology of schizophrenia will be provided by single cell datasets from the human brain that incorporate a wider range of developmental stages and brain regions, as well as spatial information 67 .…”