Medial auditory thalamus inactivation prevents acquisition and retention of eyeblink conditioning

Abstract

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated using reversible inactivation of the medial auditory thalamic nuclei (MATN) consisting of the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus (PIN). Rats were given saline or muscimol infusions into the MATN contralateral to the trained eye before each of four conditioning sessions with an auditory CS. Rats were then given four additional sessions without infusions to assess savings from the initial training. All rats were then given a retention test with a muscimol infusion followed by a recovery session. Muscimol infusions through cannula placements within 0.5 mm of the MGm prevented acquisition of eyeblink conditioned responses (CRs) and also blocked CR retention. Cannula placements more than 0.5 mm from the MATN did not completely block CR acquisition and had a partial effect on CR retention. The primary and secondary effects of MATN inactivation were examined with 2-deoxy-glucose (2-DG) autoradiography. Differences in 2-DG uptake in the auditory thalamus were consistent with the cannula placements and behavioral results. Differences in 2-DG uptake were found between groups in the ipsilateral auditory cortex, basilar pontine nuclei, and inferior colliculus. Results from this experiment indicate that the MATN contralateral to the trained eye and its projection to the pontine nuclei are necessary for acquisition and retention of eyeblink CRs to an auditory CS.Pavlovian eyeblink conditioning is an ideal paradigm for identifying the necessary and sufficient neural structures underlying associative learning (Thompson 1976(Thompson , 1983. Eyeblink conditioning is typically established by pairing a conditioned stimulus (CS) such as a tone or light with an unconditioned stimulus (US) that elicits the eyeblink reflex. An eyeblink conditioned response (CR) to the CS emerges over the course of training and occurs prior to the onset of the US. Permanent lesions, reversible inactivation, stimulation, unit recording, and neuroanatomy have been used to establish that the interpositus nucleus and cerebellar cortex are the necessary sites of learning-dependent plasticity underlying eyeblink conditioning (Thompson 2005). The basilar pontine nuclei are the proximal end of the CS pathway, which send mossy fiber input to the contralateral cerebellar cortex and interpositus nucleus (Steinmetz et al. 1986(Steinmetz et al. , 1987Lewis et al. 1987;Steinmetz 1990;Steinmetz and Sengelaub 1992;Hesslow et al. 1999;Freeman and Rabinak 2004;Freeman et al. 2005).Possible auditory inputs to the pontine nuclei that could provide auditory CS information have been proposed (Steinmetz et al. 1987;Steinmetz and Sengelaub 1992), but a systematic experimental analysis of these inputs has not been done. The ventral cochlear nucleus has a monosynaptic projection to the pontine nuclei in rats and rabbits (Steinmetz et al. 1987;Campolattaro et al. 2007), but this short-latency audit...

Stimulation of the lateral geniculate, superior colliculus, or visual cortex is sufficient for eyeblink conditioning in rats

“…However, unilateral stimulation of the LGN, SC, or VCTX in the hemisphere contralateral to the conditioned eye was sufficient for eyeblink conditioning in rats in the present study, suggesting that the necessary visual CS pathway for cerebellar learning may be primarily unilateral. Unilateral CS input has been demonstrated for the auditory CS pathway in rats, where the inputs to the PN that are necessary for eyeblink conditioning arise from the inferior colliculus and medial auditory thalamus in the hemisphere contralateral to the conditioned eye (Halverson and Freeman 2006;Campolattaro et al 2007;Halverson et al 2008). Inactivation or lesion studies are needed to determine whether the visual CS pathway for eyeblink conditioning is unilateral.…”

“…Recent studies using lesions, inactivation, stimulation, and neural tract tracing have provided evidence that the auditory CS pathway that is necessary for acquisition and retention of eyeblink conditioning is comprised of converging inputs to the medial auditory thalamic nuclei (MATN), and a direct ipsilateral projection from the MATN to the PN (Halverson and Freeman 2006;Campolattaro et al 2007;Freeman et al 2007;Halverson et al 2008). Unilateral lesions of the MATN, contralateral to the conditioned eye, block acquisition of eyeblink CRs to a tone CS but have no effect on conditioning with a light CS (Halverson and Freeman 2006).…”

“…Unilateral lesions of the MATN, contralateral to the conditioned eye, block acquisition of eyeblink CRs to a tone CS but have no effect on conditioning with a light CS (Halverson and Freeman 2006). Inactivation of the MATN with muscimol blocks acquisition and retention of CRs to an auditory CS, and decreases metabolic activity in the PN (Halverson et al 2008). The MATN has a direct projection to the PN and stimulation of the MATN supports rapid CR acquisition (Campolattaro et al 2007).…”

“…The MATN has a direct projection to the PN and stimulation of the MATN supports rapid CR acquisition (Campolattaro et al 2007). Our current model of the auditory CS pathway consists of converging inputs to the MATN, and direct unilateral thalamic input to the PN (Halverson et al 2008).…”

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

“…The latter two groups did not differ significantly from each other (P=0.356; Figure 3B). In addition, a separate oneway repeated measures ANOVA revealed that the simple main effects of session on the CR peak amplitude were significant for both the delay [F (9,63) =5.143, P<0.001] and shorttrace [F (9,72) =4.529, P<0.001] conditioned groups, but not for the long-trace conditioned group [F (9,81) =0.873, P=0.554; Figure 3B]. …”