Response Adaptation in Barrel Cortical Neurons Facilitates Stimulus Detection during Rhythmic Whisker Stimulation in Anesthetized Mice

Abstract

Rodents use rhythmic whisker movements at frequencies between 4 and 12 Hz to sense the environment that will be disturbed when the animal touches an object. The aim of this work is to study the response adaptation to rhythmic whisker stimulation trains at 4 Hz in the barrel cortex and the sensitivity of cortical neurons to changes in the timing of the stimulation pattern. Longitudinal arrays of four iridium oxide electrodes were used to obtain single-unit recordings in supragranular, granular, and infragranular neurons in urethane anesthetized mice. The stimulation protocol consisted in a stimulation train of three air puffs (20 ms duration each) in which the time interval between the first and the third stimuli was fixed (500 ms) and the time interval between the first and the second stimuli changed (regular: 250 ms; “accelerando”: 375 ms; or “decelerando” stimulation train: 125 ms interval). Cortical neurons adapted strongly their response to regular stimulation trains. Response adaptation was reduced when accelerando or decelerando stimulation trains were applied. This facilitation of the shifted stimulus was mediated by activation of NMDA receptors because the effect was blocked by AP5. The facilitation was not observed in thalamic nuclei. Facilitation increased during periods of EEG activation induced by systemic application of IGF-I, probably by activation of NMDA receptors, as well. We suggest that response adaptation is the outcome of an intrinsic cortical information processing aimed at contributing to improve the detection of “unexpected” stimuli that disturbed the rhythmic behavior of exploration.

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

“…Similarly, no significant differences were found in the number of spikes and the response latency in both animal groups. The low spontaneous firing rate and the reduced tactile responses to whisker stimulation provide strong support that recordings were obtained from pyramidal cells in the barrel cortex, as was reported previously [ 6 , 38 , 39 , 40 , 41 ].…”

“…It has been demonstrated that the insulin-like growth factor I (IGF-I) can be a potent stimulator of neuronal activity, participating in numerous brain processes (see for review [ 1 , 2 , 3 , 4 , 5 ]). Indeed, IGF-I increases the spontaneous firing rate as well as the response to afferent stimulation in target neurons [ 6 , 7 , 8 , 9 , 10 , 11 ]. Furthermore, IGF-I injection enhances fast activity in the EEG of mice and non-human primates [ 12 , 13 ].…”

“…It is known that trains of repetitive stimulation of whiskers or during whisking induce a long-lasting response facilitation in S1 neurons of rodents [ 21 , 22 , 23 , 24 ]. This response facilitation is mediated by the activation of NMDA glutamatergic receptors and increases during periods of EEG activation induced by IGF-I application [ 6 , 23 ]. However, the possible beneficial effects of IGF-I on cortical responses may be altered in pathological situations in which the circulating IGF-I signaling is decreased, such as diabetes or Alzheimer’s disease [ 2 , 25 ].…”

Reduced Insulin-Like Growth Factor-I Effects in the Basal Forebrain of Aging Mouse

“…IGF-I exerts many actions in the brain, including protection against injury, modulation of neuronal excitability, angiogenesis, or neurogenesis (see for review Fernandez and Torres-Alemán, 2012 ; Fernandez et al, 2018 ). IGF-I enhances neuronal activity in many brain areas (Carro et al, 2000 ; Gonzalez de la Vega et al, 2001 ; Kelsch et al, 2001 ; Nuñez et al, 2003 ; Barros-Zulaica et al, 2019 ; Zegarra-Valdivia et al, 2020 ). IGF-I has also been implicated in brain neurotransmitter release regulation, such as ACh neurotransmission.…”

“…In addition, it has been demonstrated that insulin-like growth factor-I (IGF-I) can be a potent stimulator of neuronal activity, participating in numerous brain processes (see for review Fernandez and Torres-Alemán, 2012 ; Fernandez et al, 2018 ). Indeed, IGF-I increases the spontaneous firing rate and response to afferent stimulation in target neurons (Carro et al, 2000 ; Nuñez et al, 2003 ; Gazit et al, 2016 ; Barros-Zulaica et al, 2019 ). We have recently demonstrated that IGF-I increases orexin neurons’ activity, located in the lateral hypothalamus, involved in controlling the circadian sleep/wake cycle (Zegarra-Valdivia et al, 2020 ).…”