Cholinesterase inhibitor, donepezil, improves visual contrast detectability in freely behaving rats

Abstract

Acetylcholine (ACh) modulates neuronal activities in extensive brain regions to play an essential role in various brain functions including attention, learning and memory, and cognition. Although ACh is known to modulate information processing in the primary visual cortex (V1) in many species including rodent, its functional role in visual ability has remained unknown. We examined whether and how ACh influences behavioral contrast detectability in rat. The detectability was assessed as the contrast sensitivity (CS) to a grating stimulus. Measurements were performed in a two-alternative forced-choice task combined with a staircase method in freely behaving rats. The contrast sensitivity function of rats under the no drug condition showed a low-pass spatial frequency (SF) tuning peaking at 0.1 cycles/degree (cpd) of SF (SF(peak)) that bottomed at 0.5 cpd (SF(bottom)), which was sensitive to the stimulus size, but to neither the temporal frequency nor orientation of the stimulus. The stimulus size was correlated with the CS only at the low SF range. The effect of donepezil on the size- and SF-dependency of the CS was examined using three stimulus conditions: an easy detectability condition with large grating at SF(peak), a difficult detectability condition with small grating at SF(peak), and an upper limit SF condition with large grating at SF(bottom). Donepezil improved the CS at SF(peak), especially in the difficult detectability condition. Therefore, we conclude that ACh plays an important role in enhancing behavioral CS at sensitive SF ranges, but not in improving the upper limit of SF.

Donepezil increases contrast sensitivity for the detection of objects in scenes

“…Participants received placebo first and nicotine (skin patch) second or the opposite. The results showed that participants were faster to detect stimuli of high intensity under nicotine (cholinergic stimulation) than under placebo, consistent with "the response gain control" [14,15,19], in which the stronger the signal input (contrast) is, the greater the facilitatory modulation is. In the present study the facilitatory effect of donepezil was larger when the input signal was strong (i.e., higher levels of contrast) consistent with ACh modulation of contrast sensitivity and signal-to-noise ratio in the visual cortex.…”

“…Soma et al [15] reported that the pharmacological activation of ACh receptors in the visual cortex of rats controls the gain in the relationship between the stimulus contrast (the intensity of the visual input) and the neuronal response; an effect called "response gain control". In the same line, Disney et al [19] showed that iontophoretic application of nicotine (a cholinergic agonist) reliably enhances visual gain in layer 4c of V1 in monkeys.…”

“…ACh modulates the contrast sensitivity, and signal-to-noise ratio of responses in the visual cortex, to enhance the detectability of a visual stimulus. For instance, Soma et al [15] examined whether ACh influences behavioral contrast detectability in rats. They measured the contrast sensitivity to a grating stimulus in freely behaving animals.…”

“…The nucleus of Meynert provides the principal cholinergic input of the cortex [11]. The primary visual cortex (V1) is a major target of cholinergic projections, and its neuronal information processing is known to be modulated by acetylcholine (ACh) in many species [12][13][14][15]. ACh modulates the contrast sensitivity, and signal-to-noise ratio of responses in the visual cortex, to enhance the detectability of a visual stimulus.…”

Neuroprotective Effects of the Extracts from the Aerial Parts of Carthamus tinctorius L. on Transient Cerebral Global Ischemia in Rats

“…Donepezil, an AChE inhibitor and most widely used treatment for Alzheimer's disease, donepezil at a dose of 5 ㎎/㎏ (oral administraion) was used as a positive control (Soma et al, 2013). Scopolamine interferes with memory and cognitive function and subsequently causes similar degrees of impairment test (Vales et al, 2005).…”