Response Facilitation Induced by Insulin-like Growth Factor-I in the Primary Somatosensory Cortex of Mice Was Reduced in Aging

Abstract

Aging is accompanied by a decline in cognition that can be due to a lower IGF-I level. We studied response facilitation induced in primary somatosensory (S1) cortical neurons by repetitive stimulation of whiskers in young and old mice. Layer 2/3 and 5/6 neurons were extracellularly recorded in young (≤ 6 months of age) and old (≥ 20 month of age) anesthetized mice. IGF-I injection in S1 cortex (10 nM; 0.2 μL) increased whisker responses in young and old animals. A stimulation train at 8 Hz induced a long-lasting response facilitation in only layer 2/3 neurons of young animals. However, all cortical neurons from young and old animals showed long-lasting response facilitation when IGF-I was applied in the S1 cortex. The reduction in response facilitation in old animals can be due to a reduction in the IGF-I receptors as was indicated by the immunohistochemistry study. Furthermore, a reduction in the performance of a whisker discrimination task was observed in old animals. In conclusion, our findings indicate that there is a reduction in the synaptic plasticity of S1 neurons during aging that can be recovered by IGF-I. Therefore, it opens the possibility of use IGF-I as a therapeutic tool to ameliorate the effects of heathy aging.

Cognitive Deficits in Aging Related to Changes in Basal Forebrain Neuronal Activity

“…An IGF-I injection in the BF elicited fast oscillatory activity in the electrocorticogram and facilitated whisker responses in the S1 cortex. These excitatory effects evoked by IGF-I decreased in old mice, probably due to a reduction in the number of IGF-I receptors, as was indicated by the immunohistochemistry studies [98,99].…”

“…An IGF-I injection in the BF elicited fast oscillatory activity in the electrocorticogram and facilitated whisker responses in the S1 cortex. These excitatory effects evoked by IGF-I decreased in old mice, probably due to a reduction in the number of IGF-I receptors, as was indicated by the immunohistochemistry studies [98,99]. According to this hypothesis, cholinergic-identified and non-identified neurons in the HDB nucleus showed a decreased response to IGF-I in old mice that provoked a reduction of cortical activity.…”

“…Thus, the activation of the IGF-IR/Akt/GSK3 intracellular pathway was reduced in old mice [116,117]. Consequently, a reduction of the IGF-I system may contribute to cognitive deficits, as has been suggested during healthy aging [1,98,99,114,116,118,119].…”

“…It is well known that IGF-I plays a key role in learning and memory processes as a potent stimulator of neuronal activity. IGF-I increases the spontaneous firing rate, as well as the response to afferent stimulation in many target neurons [98][99][100][101][102][103], and modulates excitatory synaptic transmission in many areas of the brain [104][105][106][107][108][109]. IGF-I signaling modulates the activity of calcium-calmodulin-dependent kinase 2 alpha (CaMKIIα) and mitogen activated protein kinase (MAPK/ErK) through multiple signaling pathways [110][111][112].…”

“…According to this hypothesis, cholinergic-identified and non-identified neurons in the HDB nucleus showed a decreased response to IGF-I in old mice that provoked a reduction of cortical activity. Specifically, optogenetic stimulation of cholinergic neurons located in the HDB area facilitated whisker responses in the S1 cortex through activation of muscarinic receptors [30]; this facilitation of sensory cortical responses was decreased in old mice [98,99].…”