Postnatal Development of Chloride Cotransporters in the Piriform Cortex and Its Modulation by Early Maternal Care

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Autores principales: Christell Becerra‐Flores, Enver M. Oruro, Carlos Medina‐Saldivar, Luis F. Pacheco‐Otálora, Grace E. Pardo
Formato: Artículo Open Access
Publicado: Wiley 2026
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author Christell Becerra‐Flores
Enver M. Oruro
Carlos Medina‐Saldivar
Luis F. Pacheco‐Otálora
Grace E. Pardo
author_facet Christell Becerra‐Flores
Enver M. Oruro
Carlos Medina‐Saldivar
Luis F. Pacheco‐Otálora
Grace E. Pardo
Christell Becerra‐Flores
Enver M. Oruro
Carlos Medina‐Saldivar
Luis F. Pacheco‐Otálora
Grace E. Pardo
collection Wiley Open Access
contents Postnatal Development of Chloride Cotransporters in the Piriform Cortex and Its Modulation by Early Maternal Care Christell Becerra‐Flores Enver M. Oruro Carlos Medina‐Saldivar Luis F. Pacheco‐Otálora Grace E. Pardo Developmental Psychobiology ABSTRACT Early postnatal development is a sensitive period for inhibitory maturation, during which GABAergic signaling shifts from depolarizing to hyperpolarizing as a function of the chloride cotransporters KCC2 and NKCC1. Although these cotransporters are key to inhibitory development, little is known about how early caregiving influences their maturation in cortical circuits supporting attachment learning. We characterized KCC2 and NKCC1 expression in the piriform cortex (PC) of male and female rats from postnatal (P) Day 5 to 22 and assessed their sensitivity to altered caregiving using the limited bedding and nesting (LBN) paradigm (P2–P9). Both cotransporters showed robust postnatal protein upregulation, with sex‐specific transcriptional differences for KCC2. At P15, LBN induced sex‐ and region‐dependent changes. KCC2 transcription decreased in the anterior PC of males but increased in females in the posterior PC. NKCC1 protein was reduced in both sexes with distinct anterior–posterior patterns. Using a single‐neuron Hodgkin–Huxley model with dynamic ion concentrations incorporating the measured cotransporter profiles, simulations indicated that these differences were sufficient to modify chloride homeostasis and shift GABAergic control of excitability. This multiscale approach links early alterations in caregiving to predicted functional consequences for inhibitory maturation in the PC. 10.1002/dev.70161 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/dev.70161
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spellingShingle Postnatal Development of Chloride Cotransporters in the Piriform Cortex and Its Modulation by Early Maternal Care
Christell Becerra‐Flores
Enver M. Oruro
Carlos Medina‐Saldivar
Luis F. Pacheco‐Otálora
Grace E. Pardo
Developmental Psychobiology
Postnatal Development of Chloride Cotransporters in the Piriform Cortex and Its Modulation by Early Maternal Care Christell Becerra‐Flores Enver M. Oruro Carlos Medina‐Saldivar Luis F. Pacheco‐Otálora Grace E. Pardo Developmental Psychobiology ABSTRACT Early postnatal development is a sensitive period for inhibitory maturation, during which GABAergic signaling shifts from depolarizing to hyperpolarizing as a function of the chloride cotransporters KCC2 and NKCC1. Although these cotransporters are key to inhibitory development, little is known about how early caregiving influences their maturation in cortical circuits supporting attachment learning. We characterized KCC2 and NKCC1 expression in the piriform cortex (PC) of male and female rats from postnatal (P) Day 5 to 22 and assessed their sensitivity to altered caregiving using the limited bedding and nesting (LBN) paradigm (P2–P9). Both cotransporters showed robust postnatal protein upregulation, with sex‐specific transcriptional differences for KCC2. At P15, LBN induced sex‐ and region‐dependent changes. KCC2 transcription decreased in the anterior PC of males but increased in females in the posterior PC. NKCC1 protein was reduced in both sexes with distinct anterior–posterior patterns. Using a single‐neuron Hodgkin–Huxley model with dynamic ion concentrations incorporating the measured cotransporter profiles, simulations indicated that these differences were sufficient to modify chloride homeostasis and shift GABAergic control of excitability. This multiscale approach links early alterations in caregiving to predicted functional consequences for inhibitory maturation in the PC. 10.1002/dev.70161 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Postnatal Development of Chloride Cotransporters in the Piriform Cortex and Its Modulation by Early Maternal Care
topic Developmental Psychobiology
url https://onlinelibrary.wiley.com/doi/10.1002/dev.70161