Sensitivity of the S1 neuronal calcium network to insulin and Bay‐K 8644 in vivo: Relationship to gait, motivation, and aging processes

Abstract

Neuronal hippocampal Ca2+ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer's disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca2+ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca2+ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single‐cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging‐ and Ca2+‐dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L‐type voltage‐gated Ca2+ channel modifier Bay‐K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca2+ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age.

Age‐ and sex‐dependent alterations in primary somatosensory cortex neuronal calcium network dynamics during locomotion

“…Signal processing and data extraction were accomplished using a custom MATLAB pipeline as previously described (Lin et al, 2022).…”

“…Our lab has previously described alterations in gait performance with aging that reflect on dysregulation in neuronal networks using the F344 rat model of aging, where number of active neurons and connectivity were increased with aging (Lin et al, 2022) synchronicity were noted in the anesthetized F344 rat. This is likely because the use of anesthesia has been shown to increase neuronal synchrony (Goltstein et al, 2015), possibly influencing our ability to detect age-related effects in the anesthetized rat (i.e., ceiling effect).…”

Falling Short: The Contribution of Central Insulin Receptors to Gait Dysregulation in Brain Aging

“…In the same animals, INI was also able to decrease the time taken to ambulate down a corridor during a gait behavioral task [ 137 ] perhaps indicating that the changes in ambulation were reflected by alterations in network communication. Further, in this same model, we also found that INI was able to significantly alter measures of CBF ( Figure 4 ).…”

“…Cent symbols (¢) denote Bonferroni post hoc significance ( p < 0.05) between INS and INI at the timepoints indicated. Figure reproduced from Lin et al, 2022 [ 137 ].…”

Konstruksi Motivasi Dalam Pandangan Islam

“…12 Frazier menyatakan bahwa, ada bukti yang berkembang tentang peran tujuan agama dalam fungsi manusia yang positif serta kesejahteraan subjektif. 13 Jung berpendapat bahwa agama memiliki dampak positif dan dia secara khusus mendorong praktik keagamaan tersebut. 14…”