Abstract
It has been suggested that age-related impairments in learning and memory may be due to age-related deficits in long-term potentiation of glutamatergic synaptic transmission. For example, olfactory discrimination learning is significantly affected by aging in mice and this may be due, in part, to diminished synaptic plasticity in piriform cortex. In the present study, we tested for alterations in electrophysiological properties and synaptic transmission in this simple cortical network. Whole-cell recordings were made from principal neurons in slices of anterior piriform cortex from young (3–6 months old) and old (24–28 months) C57Bl/6 mice. Miniature excitatory postsynaptic currents (mEPSCs) mediated by AMPA receptors were collected from cells in presence of tetrodotoxin (TTX) and held at -80 mV in voltage-clamp. Amplitudes of mEPSCs were significantly reduced in aged mice, suggesting that synaptic AMPA receptor expression is decreased during aging. In a second set of experiments, spontaneous excitatory postsynaptic currents (s/mEPSCs) were recorded in slices from different cohorts of young and old mice, in the absence of TTX. These currents resembled mEPSCs and were similarly reduced in amplitude in old mice. The results represent the first electrophysiological evidence for age-related declines in glutamatergic synaptic function in the mammalian olfactory system.
Highlights
Changes in the nervous system with aging are profound and mysterious
AMPA RECEPTOR-MEDIATED Miniature excitatory postsynaptic currents (mEPSCs) ARE SMALLER IN THE AGED MOUSE As described previously (Gocel and Larson, 2012), superficial pyramidal (SP) neurons held at −80 mV under voltage clamp in the presence of BMI, CPP, and TTX showed spontaneous inward currents with the characteristics of mEPSCs, in slices from both young and old mice (Figure 2A)
These events were abolished by perfusion with CNQX, confirming that they were mediated by AMPA receptors
Summary
The brain exhibits subtle alterations in cellular morphology, synaptic structure, gene expression patterns, and electrophysiological characteristics as it ages; less subtle, perhaps, are the sensory, motor, and cognitive declines that accompany the aging process. Understanding the relationships between neurobiological changes and functional outcomes is one of the fundamental challenges of aging neuroscience. Considerable progress has been made in correlating age-dependent changes in hippocampal circuitry to spatial learning and memory deficits in aging animals. Two general principles have emerged from studies of hippocampal long-term potentiation (LTP) in aged animals (Burke and Barnes, 2010): first, age-dependent effects on synaptic function are regionally heterogeneous. Electrophysiological studies using minimal stimulation suggest that “basal” synaptic potency, the average size of the postsynaptic response to a presynaptic release event (Stevens and Wang, 1994), declines with extreme age in CA1 but not dentate. LTP induction mechanisms are typically only impaired when stimulation is close to the induction threshold; LTP expression, provided that induction conditions are suprathreshold, appears normal (Burke and Barnes, 2010)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
