Classical conditioning of eyelid and mystacial vibrissae responses in conscious mice

Abstract

The murine vibrissae sensorimotor system has been scrutinized as a target of motor learning through trace classical conditioning. Conditioned eyelid responses were acquired by using weak electrical whisker-pad stimulation as conditioned stimulus (CS) and strong electrical periorbital stimulation as unconditioned stimulus (US). In addition, conditioned vibrissal protraction was obtained pairing either weak electrical whisker-pad stimulation or a tone as CS, with a strong electric shock delivered in the whisker-pad as US. This finding suggests that evolutionary pressure has selected a sensorimotor system capable of constructing conditioned responses on the basis of temporal relationships of stimuli, independently of any putative functional purpose.Classical conditioning of blink responses is widely used to explore the neural mechanisms underlying associative learning and memory storage in diverse species (Gormezano et al. 1983;Gruart et al. 1995;Bao et al. 1998;Weiss et al. 1999;Zhao et al. 1999). This conditioning is acquired after repetitive and contingent paired presentations of a neutral, conditioned stimulus (CS) and a blink-evoking, unconditioned stimulus (US).Eyeblink conditioning has been attained by using auditory, somatosensory, or visual CSs paired with an air-puff to the eye or a strong periorbital shock as USs (Gormezano et al. 1983;Paczkowski et al. 1999;Gruart et al. 2000). Das and colleagues (2001) obtained eyeblink conditioning in rabbits by using vibratory stimulation of the mystacial vibrissae as CS.The vibrissal sensorimotor system is used to scan object surfaces, extracting detailed information from the environment (Woolsey and Van der Loos 1970;Carvell et al. 1991). Both behavioral (Bermejo et al. 1996) and experience-induced cortical plasticity (Fox 2002) have been demonstrated as a result of adult whisker manipulations. Here, we examined the possibility of using stimulation of its sensory branch as CS and/or its motor branch as the generator of conditioned responses (CRs). Thus, we evaluated the acquisition of eyeblink conditioning by using electrical stimulation of the mystacial vibrissae as CS, and the acquisition of conditioned vibrissal protraction by using either electrical stimulation of the mystacial vibrissae or auditory stimulation, also as CS. Whisker-pad electrical stimulation as CS during blink conditioningAn isolated weak electrical stimulus in the whisker-pad occasionally elicited a variable-latency (∼25 to 35 msec), brief (<10 msec), low-voltage (<20 µV) blink response (Fig. 1C). When this CS was consistently paired with a strong electric shock in periorbital region (US), using a trace paradigm (w-E), the subjects gradually displayed CRs (%CR: F (9,90) = 57.321, P < 0.001; amplitude: F (9,90) = 19.635, P < 0.001) (Fig. 1A,B). Initially, these responses were brief and had variable latency (Fig. 1C); however, as the training advanced, the CRs acquired long latency and an in crescendo profile (Fig. 1C). During extinction, CR frequency progressively decreased (F (3,36) = 25.901...

Learning-dependent potentiation in the vibrissal motor cortex is closely related to the acquisition of conditioned whisker responses in behaving mice

“…In agreement with a previous report (Troncoso et al 2004), mice exposed to a trace (tone/whisker-pad-shock) conditioning paradigm acquired vibrissal CRs (Fig. 1A).…”

“…This last fact suggests that the learningdependent plastic changes described here could be due to the strengthening of cortico-cortical inputs carrying CS-related information to the vibrissal motor cortex by mechanisms that might be similar to LTP. Although the CRs reported here are apparently devoid of an obvious functional sense, the inherent plasticity of the sensorimotor system seems capable of constructing motor responses on the basis of temporal relationships of stimuli, regardless of their functional purpose (Troncoso et al 2004). In 4 Corresponding author.…”

“…The stimulus dispensers (either a loudspeaker or an isolation unit) were commanded by a computer-controlled pulse generator (EMDPP, Cibertec). Further details of these experimental procedures have been detailed elsewhere (Troncoso et al 2004). …”

“…Moreover, in a preceding report, we found that the classical conditioning of vibrissal protraction responses to a tone, used as a CS, in conscious mice could be a useful model to the study of learninginduced changes in the facial motor system (Troncoso et al 2004). In the present experiments, we used a trace conditioning paradigm, in which the CS consisted of a binaural tone, whilst the unconditioned stimulus (US) was an electrical shock presented to the right whisker-pad.…”

Behavioral verification of associative learning in whisker-related fear conditioning in mice

“…Moreover, several methods of sensory training in which the vibrissae system is engaged in learning have been developed, such as the gap-crossing task (Barnéoud et al 1991, Troncoso et al 2004, object localization tasks (e.g. O'Connor et al 2010, Kuhlman et al 2014), the texture discrimination task (Guic-Robles et al 1989, Cybulska-Klosowicz and Kossut 2001, Wu et al 2013, Zuo et al 2015, and the vibrotactile frequencies discrimination task (e.g.…”