Altered Network Timing in the CA3-CA1 Circuit of Hippocampal Slices from Aged Mice

Abstract

Network patterns are believed to provide unique temporal contexts for coordinating neuronal activity within and across different regions of the brain. Some of the characteristics of network patterns modeled in vitro are altered in the CA3 or CA1 subregions of hippocampal slices from aged mice. CA3–CA1 network interactions have not been examined previously. We used slices from aged and adult mice to model spontaneous sharp wave ripples and carbachol-induced gamma oscillations, and compared measures of CA3–CA1 network timing between age groups. Coherent sharp wave ripples and gamma oscillations were evident in the CA3–CA1 circuit in both age groups, but the relative timing of activity in CA1 stratum pyramidale was delayed in the aged. In another sample of aged slices, evoked Schaffer collateral responses were attenuated in CA3 (antidromic spike amplitude) and CA1 (orthodromic field EPSP slope). However, the amplitude and timing of spontaneous sharp waves recorded in CA1 stratum radiatum were similar to adults. In both age groups unit activity recorded juxtacellularly from unidentified neurons in CA1 stratum pyramidale and stratum oriens was temporally modulated by CA3 ripples. However, aged neurons exhibited reduced spike probability during the early cycles of the CA3 ripple oscillation. These findings suggest that aging disrupts the coordination of patterned activity in the CA3–CA1 circuit.

Hippocampal sharp waves and ripples: Effects of aging and modulation by NMDA receptors and L-type Ca2+ channels

“…The finding of reduced ripples in old animals is in agreement with previous observations showing reduced energy or power of the ripple oscillation in aged mice (Hermann et al, 2009, Kanak et al, 2013. Furthermore, in keeping with previous in vivo observations (Gerrard et al, 2001) we found that the occurrence and the amplitude of SWRs are similar between adult and old animals.…”

Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

“…Since ageing is associated with loss of presynaptic terminals 8 9 and altered neuronal functionality 31 , we explored the possibility that the montelukast-induced effect on cognitive function was related to these parameters. Indeed, synaptic density (synaptophysin positive area) was significantly reduced in the hippocampus of old rats, but only slightly and not significantly in the cortex.…”

Neurodegenerative Diseases – Is Metabolic Deficiency the Root Cause?

“…In rodent studies, severe mitochondrial damages were observed in the CA1 region when compared to the CA3 region in post-ischemic conditions (Radenovic et al, 2011). Thus, neurons in the CA1 region are more susceptible to mitochondrial damage and oxidative stress when compared to the CA3 region (Kanak et al, 2013). Human gene expression studies reveal that genes involved in energy metabolism were downregulated in AD.…”

“…During aging, the CA3 region is hyperactivated, whereas the CA1 region showed a reduced firing rate (Kanak et al, 2013;Simkin et al, 2015;Oh et al, 2016). As we age, overexcitation of excitatory neurons leads to an excessive accumulation of glutamate in the synaptic cleft (Esposito et al, 2013;Assefa et al, 2018), which results in glutamate-induced toxicity.…”