Zobraziť v EDS

Aging-related adaptations of metabotropic glutamate receptors within the CA3 region of the rat hippocampus.

Uložené v:
Podrobná bibliografia
Názov: Aging-related adaptations of metabotropic glutamate receptors within the CA3 region of the rat hippocampus.
Autori: Galván, Emilio J.1,2 (AUTHOR), Griego, Ernesto1 (AUTHOR) ernesto.griegomelo@einsteinmed.edu
Zdroj: Neurobiology of Aging. Dec2025, Vol. 156, p111-122. 12p.
Predmety: *AGING, *HIPPOCAMPUS (Brain), *GLUTAMATE receptors, *COGNITION disorders, *ACTION potentials, *PYRAMIDAL neurons, *NEUROPLASTICITY
Abstrakt: The physiological decline associated with aging is often accompanied by a progressive deterioration in cognitive processing abilities driven by a series of cellular dysfunctions that remain poorly understood. In the hippocampus, a critical area for learning and memory, aging affects the functional expression of ionotropic and metabotropic receptors, including the metabotropic glutamate receptors (mGluRs). mGluRs play a critical role in multiple cellular functions, including modulation of ion channels and intrinsic excitability, synaptic transmission, and induction of synaptic plasticity, processes considered part of the cellular substrates for learning and memory. This study used patch-clamp recordings and pharmacological tools in acute hippocampal slices to uncover the aging-related disruption in the mGluR-dependent modulation of area CA3 pyramidal neurons. Pharmacological stimulation of group I mGluRs triggers rhythmic firing discharge in CA3 pyramidal neurons of young rats (5 ± 1 weeks of age) and a reduction in the afterhyperpolarization. By contrast, in older adult rats (20–24 months of age), stimulation of group I mGluRs causes a switch from afterhyperpolarization to an afterdepolarization plateau that eases a persistent but non-rhythmic firing discharge. In young animals, postsynaptic activation of group II mGluRs enhances the intrinsic excitability of CA3 pyramidal neurons, and an exacerbated response is observed in older adult rats. By contrast, in older adult animals, the presynaptic inhibition of glutamate release by pharmacological stimulation of group II mGluRs from mossy fibers was significantly reduced. These findings support the notion of older adult-related changes in the functional expression of mGluRs within the hippocampal area CA3 that may contribute to the cognitive alterations commonly associated with aging. • Aging disrupts the oscillatory activity of CA3 neurons mediated by group I mGluRs. • Aging increases the firing of CA3 neurons in response to group I mGluRs activation. • Aging reduces the effects of group II mGluRs on glutamate release from MF boutons. • Postsynaptic depolarization of CA3 neurons by group II mGluRs is enhanced by aging. [ABSTRACT FROM AUTHOR]
Databáza: Academic Search Index
Popis
Abstrakt:The physiological decline associated with aging is often accompanied by a progressive deterioration in cognitive processing abilities driven by a series of cellular dysfunctions that remain poorly understood. In the hippocampus, a critical area for learning and memory, aging affects the functional expression of ionotropic and metabotropic receptors, including the metabotropic glutamate receptors (mGluRs). mGluRs play a critical role in multiple cellular functions, including modulation of ion channels and intrinsic excitability, synaptic transmission, and induction of synaptic plasticity, processes considered part of the cellular substrates for learning and memory. This study used patch-clamp recordings and pharmacological tools in acute hippocampal slices to uncover the aging-related disruption in the mGluR-dependent modulation of area CA3 pyramidal neurons. Pharmacological stimulation of group I mGluRs triggers rhythmic firing discharge in CA3 pyramidal neurons of young rats (5 ± 1 weeks of age) and a reduction in the afterhyperpolarization. By contrast, in older adult rats (20–24 months of age), stimulation of group I mGluRs causes a switch from afterhyperpolarization to an afterdepolarization plateau that eases a persistent but non-rhythmic firing discharge. In young animals, postsynaptic activation of group II mGluRs enhances the intrinsic excitability of CA3 pyramidal neurons, and an exacerbated response is observed in older adult rats. By contrast, in older adult animals, the presynaptic inhibition of glutamate release by pharmacological stimulation of group II mGluRs from mossy fibers was significantly reduced. These findings support the notion of older adult-related changes in the functional expression of mGluRs within the hippocampal area CA3 that may contribute to the cognitive alterations commonly associated with aging. • Aging disrupts the oscillatory activity of CA3 neurons mediated by group I mGluRs. • Aging increases the firing of CA3 neurons in response to group I mGluRs activation. • Aging reduces the effects of group II mGluRs on glutamate release from MF boutons. • Postsynaptic depolarization of CA3 neurons by group II mGluRs is enhanced by aging. [ABSTRACT FROM AUTHOR]
ISSN:01974580
DOI:10.1016/j.neurobiolaging.2025.08.008