Abstract
Variations in early life maternal care modulate hippocampal development to program distinct emotional–cognitive phenotypes that persist into adulthood. Adult rat offspring that received low compared with high levels of maternal licking and grooming (low LG offspring) in early postnatal life show reduced long term potentiation (LTP) and impaired hippocampal-dependent memory, suggesting a ‘detrimental’ maternal effect on neural development. However, these studies focused uniquely on the dorsal hippocampus. Emerging evidence suggests a distinct role of the ventral hippocampus in mediating aggression, anxiety, and fear-memory formation, which are enhanced in low LG offspring. We report that variations in maternal care in the rat associate with opposing effects on hippocampal function in the dorsal and ventral hippocampus. Reduced pup licking associated with suppressed LTP formation in the dorsal hippocampus, but enhanced ventral hippocampal LTP. Ventral hippocampal neurons in low LG offspring fired action potentials at lower threshold voltages that were of larger amplitude and faster rise rate in comparison with those in high LG offspring. Furthermore, recordings of excitatory postsynaptic potential-to-spike coupling (E-S coupling) revealed an increase in excitability of ventral hippocampal CA1 neurons in low LG offspring. These effects do not associate with changes in miniature excitatory postsynaptic currents or paired-pulse facilitation, suggesting a specific effect of maternal care on intrinsic excitability. These findings suggest region-specific influences of maternal care in shaping neural development and synaptic plasticity.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Adhikari A, Topiwala MA, Gordon JA (2010). Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety. Neuron 65: 257–269.
Bagot RC, Tse YC, Nguyen HB, Wong AS, Meaney MJ, Wong TP (2012a). Maternal care influences hippocampal N-methyl-D-aspartate receptor function and dynamic regulation by corticosterone in adulthood. Biol Psychiatry 75: 491–498.
Bagot RC, van Hasselt FN, Champagne DL, Meaney MJ, Krugers HJ, Joels M (2009). Maternal care determines rapid effects of stress mediators on synaptic plasticity in adult rat hippocampal dentate gyrus. Neurobiol Learn Mem 92: 292–300.
Bagot RC, Zhang TY, Wen X, Nguyen TT, Nguyen HB, Diorio J et al (2012b). Variations in postnatal maternal care and the epigenetic regulation of metabotropic glutamate receptor 1 expression and hippocampal function in the rat. Proc Natl Acad Sci USA 109 (Suppl 2): 17200–17207.
Bannerman DM, Deacon RM, Offen S, Friswell J, Grubb M, Rawlins JN (2002). Double dissociation of function within the hippocampus: spatial memory and hyponeophagia. Behav Neurosci 116: 884–901.
Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB et al (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299: 1291–1305.
Bliss TV, Collingridge GL (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31–39.
Bredy TW, Humpartzoomian RA, Cain DP, Meaney MJ (2003). Partial reversal of the effect of maternal care on cognitive function through environmental enrichment. Neuroscience 118: 571–576.
Bredy TW, Zhang TY, Grant RJ, Diorio J, Meaney MJ (2004). Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression. Eur J Neurosci 20: 1355–1362.
Caldji C, Tannenbaum B, Sharma S, Francis D, Plotsky PM, Meaney MJ (1998). Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat. Proc Natl Acad Sci USA 95: 5335–5340.
Cenquizca LA, Swanson LW (2007). Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex. Brain Res Rev 56: 1–26.
Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER et al (2008). Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 28: 6037–6045.
Champagne FA, Francis DD, Mar A, Meaney MJ (2003). Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav 79: 359–371.
Champagne FA, Meaney MJ (2006). Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol Psychiatry 59: 1227–1235.
Chavez-Noriega LE, Bliss TV, Halliwell JV (1989). The EPSP-spike (E-S) component of long-term potentiation in the rat hippocampal slice is modulated by GABAergic but not cholinergic mechanisms. Neurosci Lett 104: 58–64.
Collingridge GL, Kehl SJ, McLennan H (1983). Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol 334: 33–46.
Collishaw S, Pickles A, Messer J, Rutter M, Shearer C, Maughan B (2007). Resilience to adult psychopathology following childhood maltreatment: evidence from a community sample. Child Abuse Negl 31: 211–229.
Dingemanse NJ, Both C, Drent PJ, Tinbergen JM (2004). Fitness consequences of avian personalities in a fluctuating environment. Proc Biol Sci 271: 847–852.
Dougherty KA, Islam T, Johnston D (2012). Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral hippocampus. J Physiol 590 (Pt 22): 5707–5722.
Englund M, Hyllienmark L, Brismar T (2011). Effect of valproate, lamotrigine and levetiracetam on excitability and firing properties of CA1 neurons in rat brain slices. Cell Mol Neurobiol 31: 645–652.
Fanselow MS, Dong HW (2010). Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65: 7–19.
Farrington DP, Gallagher B, Morley L St, Ledger RJ, West DJ (1988). Are there any successful men from criminogenic backgrounds? Psychiatry 51: 116–130.
Felix-Ortiz AC, Beyeler A, Seo C, Leppla CA, Wildes CP, Tye KM (2013). BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79: 658–664.
Gee DG, Gabard-Durnam LJ, Flannery J, Goff B, Humphreys KL, Telzer EH et al (2013). Early developmental emergence of human amygdala-prefrontal connectivity after maternal deprivation. Proc Natl Acad Sci USA 110: 15638–15643.
Haapasalo J, Tremblay RE (1994). Physically aggressive boys from ages 6 to 12: family background, parenting behavior, and prediction of delinquency. J Consult Clin Psychol 62: 1044–1052.
Kheirbek MA, Drew LJ, Burghardt NS, Costantini DO, Tannenholz L, Ahmari SE et al (2013). Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus. Neuron 77: 955–968.
Kjelstrup KG, Tuvnes FA, Steffenach HA, Murison R, Moser EI, Moser MB (2002). Reduced fear expression after lesions of the ventral hippocampus. Proc Natl Acad Sci USA 99: 10825–10830.
Landers MS, Sullivan RM (2012). The development and neurobiology of infant attachment and fear. Dev Neurosci 34: 101–114.
Liu D, Diorio J, Day JC, Francis DD, Meaney MJ (2000). Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci 3: 799–806.
Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F (1983). Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature 305: 719–721.
Magee JC, Johnston D (1997). A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275: 209–213.
Maggio N, Segal M (2007). Striking variations in corticosteroid modulation of long-term potentiation along the septotemporal axis of the hippocampus. J Neurosci 27: 5757–5765.
Maggio N, Segal M (2011). Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress. Biol Psychiatry 69: 748–753.
Maggio N, Segal M (2012). Steroid modulation of hippocampal plasticity: switching between cognitive and emotional memories. Front Cell Neurosci 6: 12.
Menard JL, Champagne DL, Meaney MJ (2004). Variations of maternal care differentially influence 'fear' reactivity and regional patterns of cFos immunoreactivity in response to the shock-probe burying test. Neuroscience 129: 297–308.
Menard JL, Hakvoort RM (2007). Variations of maternal care alter offspring levels of behavioural defensiveness in adulthood: evidence for a threshold model. Behav Brain Res 176: 302–313.
Miyakawa H, Ross WN, Jaffe D, Callaway JC, Lasser-Ross N, Lisman JE et al (1992). Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels. Neuron 9: 1163–1173.
Moser MB, Moser EI, Forrest E, Andersen P, Morris RG (1995). Spatial learning with a minislab in the dorsal hippocampus. Proc Natl Acad Sci USA 92: 9697–9701.
O'Steen S, Cullum AJ, Bennett AF (2002). Rapid evolution of escape ability in Trinidadian guppies (Poecilia reticulata). Evolution 56: 776–784.
Richmond MA, Yee BK, Pouzet B, Veenman L, Rawlins JN, Feldon J et al (1999). Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning. Behav Neurosci 113: 1189–1203.
Shanks N, Windle RJ, Perks PA, Harbuz MS, Jessop DS, Ingram CD et al (2000). Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function and predisposition to inflammation. Proc Natl Acad Sci USA 97: 5645–5650.
Squire LR, Alvarez P (1995). Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr Opin Neurobiol 5: 169–177.
Swanson LW, Cowan WM (1977). An autoradiographic study of the organization of the efferent connections of the hippocampal formation in the rat. J Comp Neurol 172: 49–84.
Tang CM, Margulis M, Shi QY, Fielding A (1994). Saturation of postsynaptic glutamate receptors after quantal release of transmitter. Neuron 13: 1385–1393.
Weaver IC, Meaney MJ, Szyf M (2006). Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci USA 103: 3480–3485.
Westenbroek RE, Merrick DK, Catterall WA (1989). Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons. Neuron 3: 695–704.
Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006). Learning induces long-term potentiation in the hippocampus. Science 313: 1093–1097.
Xie X, Lancaster B, Peakman T, Garthwaite J (1995). Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA Na+ channels and with native Na+ channels in rat hippocampal neurones. Pflugers Arch 430: 437–446.
Young EA, Abelson JL, Curtis GC, Nesse RM (1997). Childhood adversity and vulnerability to mood and anxiety disorders. Depress Anxiety 5: 66–72.
Yu XM, Salter MW (1998). Gain control of NMDA-receptor currents by intracellular sodium. Nature 396: 469–474.
Acknowledgements
We thank Alice S. Wong for assistance with immunoblotting and Dr. Yiu Chung Tse for assistance with electrophysiology.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Supplementary Information accompanies the paper on the Neuropsychopharmacology website
Rights and permissions
About this article
Cite this article
Nguyen, HB., Bagot, R., Diorio, J. et al. Maternal Care Differentially Affects Neuronal Excitability and Synaptic Plasticity in the Dorsal and Ventral Hippocampus. Neuropsychopharmacol 40, 1590–1599 (2015). https://doi.org/10.1038/npp.2015.19
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/npp.2015.19
This article is cited by
-
Nurture outpaces nature: fostering with an attentive mother alters social dominance in a mouse model of stress sensitivity
Molecular Psychiatry (2023)
-
Prenatal dexamethasone exposure induces anxiety- and depressive-like behavior of male offspring rats through intrauterine programming of the activation of NRG1-ErbB4 signaling in hippocampal PV interneurons
Cell Biology and Toxicology (2023)
-
Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis
Translational Psychiatry (2021)
-
Consequences of prenatal exposure to valproic acid in the socially monogamous prairie voles
Scientific Reports (2019)
-
Maternal sensitivity predicts anterior hippocampal functional networks in early childhood
Brain Structure and Function (2019)