Associative Plasticity in the Medial Auditory Thalamus and Cerebellar Interpositus Nucleus during Eyeblink Conditioning

Abstract

Eyeblink conditioning, a type of associative motor learning, requires the cerebellum. The medial auditory thalamus is a necessary source of stimulus input to the cerebellum during auditory eyeblink conditioning. Nothing is currently known about interactions between the thalamus and cerebellum during associative learning. In the current study, neuronal activity was recorded in the cerebellar interpositus nucleus and medial auditory thalamus simultaneously from multiple tetrodes during auditory eyeblink conditioning to examine the relative timing of learning-related plasticity within these interconnected areas. Learning-related changes in neuronal activity correlated with the eyeblink conditioned response were evident in the cerebellum before the medial auditory thalamus over the course of training and within conditioning trials, suggesting that thalamic plasticity may be driven by cerebellar feedback. Short-latency plasticity developed in the thalamus during the first conditioning session and may reflect attention to the conditioned stimulus. Extinction training resulted in a decrease in learning-related activity in both structures and an increase in inhibition within the cerebellum. A feedback projection from the cerebellar nuclei to the medial auditory thalamus was identified, which may play a role in learning by facilitating stimulus input to the cerebellum via the thalamo-pontine projection.

Medial auditory thalamus is necessary for acquisition and retention of eyeblink conditioning to cochlear nucleus stimulation

“…Learning-dependent cerebellar feedback to MATN may enhance thalamic output to the LPN related to the stimulus used in training and facilitate further plasticity in the cerebellum (Halverson et al 2010). The MATN, along with auditory cortex, is also part of the auditory pathway necessary for amygdaladependent fear conditioning (Romanski and LeDoux 1992).…”

“…After repeated CS -US presentations, an adaptive eyeblink conditioned response (CR) emerges prior to US onset. Converging lines of evidence indicate that the cerebellum, specifically the interpositus nucleus and cerebellar cortex, are essential sites of memory formation and storage for this task (McCormick et al 1982;McCormick and Thompson 1984a,b;Yeo et al 1985;Freeman et al 1995Freeman et al , 2005Perrett and Mauk 1995;Krupa and Thompson 1997;Garcia and Mauk 1998;Nicholson and Freeman 2002;Jirenhed et al 2007;Halverson et al 2010). However, the specific anatomical pathway by which critical auditory CS inputs from cochlear nucleus (CN) reach this cerebellar circuit during learning are currently unclear.…”

“…The monosynaptic auditory pathway from the CN to the lateral pontine nuclei (LPN) has been suggested as a possible pathway relaying auditory information to the cerebellum (Steinmetz et al 1987), but has not been manipulated experimentally. Projections from CN to LPN and other auditory structures are primarily contralateral, the CN also has polysynaptic paths to additional nuclei within the auditory system which then target LPN (Campolattaro et al 2007;Halverson et al 2010). These connections are through auditory structures such as the medial auditory thalamic nuclei (MATN), including the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior interlaminar nucleus (PIN) (Malmierca et al 2002;Halverson et al 2010).…”

“…Projections from CN to LPN and other auditory structures are primarily contralateral, the CN also has polysynaptic paths to additional nuclei within the auditory system which then target LPN (Campolattaro et al 2007;Halverson et al 2010). These connections are through auditory structures such as the medial auditory thalamic nuclei (MATN), including the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior interlaminar nucleus (PIN) (Malmierca et al 2002;Halverson et al 2010). The unilateral projection from MATN to the LPN is a necessary and sufficient cerebellar input for acquisition and expression of auditory eyeblink conditioning Freeman 2006, 2010a;Campolattaro et al 2007;Halverson et al 2008).…”

Extinction, reacquisition, and rapid forgetting of eyeblink conditioning in developing rats

“…The cerebellum receives conditioned stimulus (CS) information from the pontine nuclei via the middle cerebellar peduncle (MCP) (Steinmetz et al , 1987Steinmetz 1990), and unconditioned stimulus (US) information is transmitted to the cerebellum via climbing fiber projections from the inferior olive (McCormick et al 1985;Mauk et al 1986). Learning-related plasticity is driven by the convergence of sufficiently strong CS and US inputs to the cerebellum, and feedback from the cerebellum to parts of the CS and US pathways is critical for the facilitation and maintenance of the eyeblink conditioned response (CR) (Mauk and Donegan 1997;Halverson et al 2010). The well-defined neural circuitry characterized in adult subjects provided a "roadmap" for identifying sites of developmental change that underlie the ontogeny of eyeblink conditioning (cf., Freeman 2010).…”