Pharmacological Mechanisms of Cortical Enhancement Induced by the Repetitive Pairing of Visual/Cholinergic Stimulation

Abstract

Repetitive visual training paired with electrical activation of cholinergic projections to the primary visual cortex (V1) induces long-term enhancement of cortical processing in response to the visual training stimulus. To better determine the receptor subtypes mediating this effect the selective pharmacological blockade of V1 nicotinic (nAChR), M1 and M2 muscarinic (mAChR) or GABAergic A (GABAAR) receptors was performed during the training session and visual evoked potentials (VEPs) were recorded before and after training. The training session consisted of the exposure of awake, adult rats to an orientation-specific 0.12 CPD grating paired with an electrical stimulation of the basal forebrain for a duration of 1 week for 10 minutes per day. Pharmacological agents were infused intracortically during this period. The post-training VEP amplitude was significantly increased compared to the pre-training values for the trained spatial frequency and to adjacent spatial frequencies up to 0.3 CPD, suggesting a long-term increase of V1 sensitivity. This increase was totally blocked by the nAChR antagonist as well as by an M2 mAChR subtype and GABAAR antagonist. Moreover, administration of the M2 mAChR antagonist also significantly decreased the amplitude of the control VEPs, suggesting a suppressive effect on cortical responsiveness. However, the M1 mAChR antagonist blocked the increase of the VEP amplitude only for the high spatial frequency (0.3 CPD), suggesting that M1 role was limited to the spread of the enhancement effect to a higher spatial frequency. More generally, all the drugs used did block the VEP increase at 0.3 CPD. Further, use of each of the aforementioned receptor antagonists blocked training-induced changes in gamma and beta band oscillations. These findings demonstrate that visual training coupled with cholinergic stimulation improved perceptual sensitivity by enhancing cortical responsiveness in V1. This enhancement is mainly mediated by nAChRs, M2 mAChRs and GABAARs. The M1 mAChR subtype appears to be involved in spreading the enhancement of V1 cortical responsiveness to adjacent neurons.

Stability in the Face of Change: Lifelong Experience-Dependent Plasticity in the Sensory Cortex

“…Progress is hampered by lack of appropriate models of associative and passive learning in developing and adult experimental animals, respectively. Passive learning in adult animals has been reported (Cooke and Bear, 2010), but some forms also require cholinergic signaling (Gavornik and Bear, 2014;Kang et al, 2015). On the other hand, plasticity during vocal learning in juvenile birds may require inputs from the frontal areas, suggesting that top-down modulation can occur before the critical periods close (Puzerey et al, 2018).…”

Potential roles of cholinergic modulation in the neural coding of location and movement speed

“…This also reduced the extent of spatial integration, evident by a shift of a neuron’s preferred length toward shorter bars and a concomitant decrease in its spatial summation area (Roberts et al, 2005). Activation of cholinergic receptors also causes long-term enhancement of the magnitude of visual evoked potentials (Kang and Vaucher, 2009; Kang et al, 2015) and the behavioral sensitivity to specific visual orientations (Kang et al, 2014). Manipulations of cholinergic input also influence attentional modulation in visual cortex.…”

“…Changes in the relative balance of thalamic input and synaptic feedback could underlie the fact that knockout of specific muscarinic receptors reduces contrast sensitivity and frequency selectivity in V1 as well as altering receptive field size (Groleau et al, 2014; Groleau et al, 2015). Cholinergic modulation has also been shown to cause long-term enhancement of visual evoked potential and behavioural sensitivity (Kang and Vaucher, 2009; Kang et al, 2014; Kang et al, 2015) that could be relevant to the coding of visual cues for spatial location.…”

Cell-specific modulation of plasticity and cortical state by cholinergic inputs to the visual cortex

“…Subsequent studies have shown that co-application of ACh or muscarinic agonists with glutamate can induce a prolonged increase in response to glutamate in somatosensory cortical neurons (Lin and Phillis, 1991; Metherate et al, 1987). When the application of ACh or electrical stimulation of BF is paired with sensory stimulation in the somatosensory (Donoghue and Carroll, 1987; Howard III and Simons, 1994; Lamour et al, 1988; Metherate et al, 1987; Rasmusson and Dykes, 1988; Tremblay et al, 1990a, b), auditory cortex (Bakin and Weinberger, 1996; Dimyan and Weinberger, 1999; Edeline et al, 1994; Kilgard and Merzenich, 1998a, b; Kilgard et al, 2001), and visual cortex (Kang et al, 2014a; Kang et al, 2015), prolonged enhanced responses to the paired sensory stimuli are observed, often along with changes in behavior (Kang et al, 2014b). These studies have also revealed that cholinergic antagonists cannot reverse the prolonged changes, thereby confirming that the induction but not maintenance of prolonged changes requires ACh (Lamour et al, 1988).…”