Increased intrinsic excitability and decreased synaptic inhibition in aged somatosensory cortex pyramidal neurons

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

“…Two prior studies investigating changes in neuronal excitability with age showed increased excitability in cerebral networks (V1 and S1), yet did not identify changes in the AHP (Hickmott & Dinse, 2013;Popescu et al, 2021). A third study also recorded neurons of S1 layers 2/3 and layer 5 in vivo did not identify significant AHPs in layers 2/3 (Zhao et al, 2016).…”

“…Work in the clinic has reported significant increases in S1 excitability concomitant with impaired tactile acuity in aged individuals (Lenz et al, 2012) along with altered cortical-proprioceptive processing with aging (Piitulainen et al, 2018) and increased beta band suppression in response to a proprioceptive stimulus that is correlated with decreased sensorimotor function (Bardouille et al, 2019;Walker et al, 2020). Evidence in animal models support these findings of increased neuronal S1 excitability with aging that is perhaps mediated by altered GABAergic innervation (Hickmott & Dinse, 2013;Popescu et al, 2021;Spengler et al, 1995). In contrast, other work has shown age-dependent decreases in functional connectivity in older, cognitively impaired, anesthetized rats (Ash et al, 2016), while another group reported that although electrophysiological measures in young and old mice showed a decrease in gamma and theta activity with age, overall neuronal excitability remained unchanged (Jessen et al, 2017).…”

“…Despite this, basic research investigating age‐related degradation in these regions, such as neuronal circuits in the dorsomedial striatum or S1, is limited. For example, some studies have shown age‐dependent changes in excitability likely mediated by increased inhibitory post‐synaptic currents in deeper layers (layers 3–5) of S1, with no change in the slow afterhyperpolarization (AHP) (Hickmott & Dinse, 2013; Popescu et al, 2021). Recently, one study comparing AHP amplitudes between layers 2/3 and layer 5 S1 neurons in the C57BL/6 mouse did not provide evidence of significant AHPs in layers 2/3 (Zhao et al, 2016).…”

Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice

“…Although not being pursued in this study, the results from p53KO mice are in many aspects opposed to the results that our laboratory has observed over the recent years from L5 pyramidal neurons in aged mice, i.e., hyperexcitability (Popescu et al, 2021 ), and increased density and TOR of dendritic spines (Mostany et al, 2013 ; Voglewede et al, 2019 ). Together with reports indicating an increased expression of p53 in aged human cells (Kulju and Lehman, 1995 ; Bitto et al, 2010 ), our data may suggest an increased expression of this transcription factor in aged neurons.…”

“…This stagnancy of the remodeling of dendritic spines may be a consequence of the deficient excitatory drive of these neurons detected in our electrophysiology assessments. Also, based on our previous studies in aged mice where the inhibitory function is declined and the baseline TOR of dendritic spines is increased (Mostany et al, 2013 ; Voglewede et al, 2019 ; Popescu et al, 2021 ), we speculate that an increase in inhibitory drive may be altering the normal dynamics of dendritic spines in p53KO mice. After whisker stimulation, the TOR of spines increased in WT mice, as we have shown previously (Alexander et al, 2018 ; Voglewede et al, 2019 ).…”