Medial auditory thalamic stimulation as a conditioned stimulus for eyeblink conditioning in rats

Abstract

The neural pathways that convey conditioned stimulus (CS) information to the cerebellum during eyeblink conditioning have not been fully delineated. It is well established that pontine mossy fiber inputs to the cerebellum convey CS-related stimulation for different sensory modalities (e.g., auditory, visual, tactile). Less is known about the sources of sensory input to the pons that are important for eyeblink conditioning. The first experiment of the current study was designed to determine whether electrical stimulation of the medial auditory thalamic nuclei is a sufficient CS for establishing eyeblink conditioning in rats. The second experiment used anterograde and retrograde tract tracing techniques to assess neuroanatomical connections between the medial auditory thalamus and pontine nuclei. Stimulation of the medial auditory thalamus was a very effective CS for eyeblink conditioning in rats, and the medial auditory thalamus has direct ipsilateral projections to the pontine nuclei. The results suggest that the medial auditory thalamic nuclei and their projections to the pontine nuclei are components of the auditory CS pathway in eyeblink conditioning.A primary emphasis in neurobiological analyses of Pavlovian eyeblink conditioning has been on identifying the anatomical sites and cellular mechanisms of memory storage (Christian and Thompson 2003;Thompson 2005). Less emphasis has been placed on identifying the neural pathways that conduct stimulation from conditioned stimuli to the sites of memory induction and retention. The cerebellum is the anatomical site of memory storage in Pavlovian eyeblink (eyelid and nictitating membrane movement) conditioning (Christian and Thompson 2003;Thompson 2005;Ohyama et al. 2006). Cerebellar function may be influenced by processes occurring within its sensory input pathways, interactions among components of the input pathways, and sources of feedback to the input pathways (Clark et al. 1997;Bao et al. 2000;Medina et al. 2002). A full characterization of the sensory input pathways to the cerebellum necessary for motor learning is, therefore, critical for developing a comprehensive understanding of cerebellar function. Identification of sensory input pathways to the cerebellum is also critical for elucidating the mechanisms underlying the ontogeny of motor learning (Freeman et al. 2005).Several key components of the conditioned stimulus (CS) pathway in eyeblink conditioning have been identified using lesion, inactivation, unit recording, stimulation, and tract tracing techniques (Steinmetz et al. 1986(Steinmetz et al. , 1987(Steinmetz et al. , 1989Lewis et al. 1987;Knowlton and Thompson 1988;Steinmetz 1990;Steinmetz and Sengelaub 1992;Gould et al. 1993;Tracy et al. 1998;Hesslow et al. 1999;Bao et al. 2000;Freeman and Rabinak 2004;Freeman et al. 2005). The pontine mossy fiber projection to the cerebellum is necessary for eyeblink conditioning with CSs of different modalities and stimulation of the pontine nuclei or the middle cerebellar peduncle is sufficient for eyeblink condit...

Evaluation of bidirectional interstimulus interval (ISI) shift in auditory delay eye-blink conditioning in healthy humans

“…While there are projections from auditory cortices to the pontine (Knowlton et al, 1993), it appears that an intact auditory cortex is not necessary for conditioning to occur (Knowlton & Thompson, 1992;Oakley & Russell, 1977). Instead, the data suggest that the primary pathways of CS entry into the pontine nuclei originate from the cochlear nuclei (Campolattaro et al, 2007;Gould et al, 1993;Steinmetz et al, 1987), inferior colliculus , and medial auditory thalamus (Campolattaro et al, 2007). While these ideas are speculative, the lack of N100 and P200 learning-related associations could reflect the possibility that auditory cortex is not necessary for normal CR acquisition in humans.…”

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

“…For instance, lesions of the visual cortex did not prevent acquisition of CRs with a light CS [73] , suggesting that the visual cortex is not involved in the process of CR acquisition, whereas stimulation of the visual cortex can be successfully used as a CS to establish CR [34] . Moreover, although lesions of the pretectal nuclei [73] and hippocampus [22][23][24]68] retarded acquisition of eyeblink conditioning, stimulation of the anterior pretectal nucleus [11] and of the CA1 layer of hippocampus [74] can not be served as effective CSs for establishing eyeblink conditioning. Therefore, the present results only suggest that electrical stimulation of mPFC is a very effective and sufficient CS for establishing eyeblink conditioning, and that it is dependent on the cerebellar interpositus nucleus, but can not be interpreted as providing evidence that mPFC is critically involved in DEC, short TEC, or long TEC.…”

“…The current was then turned down in 5-µA increments until there was no observable behavioral response. Typical behavioral responses observed from the test stimulation included movements of the eyelid, eye, ear and/ or head [8,11,14,58] . In most of the cases (28/37) in the present experiment, the threshold stimulation was between 50-120 µA.…”

“…The electrical stimulation parameters were chosen based on the recent studies [8,11,14,58] . The stimulation intensity for each guinea pig was set carefully before training by increasing the test current until a behavioral response was observed to avoid biasing the experimental results through an electrical startle response and a spreading of the electrical stimulation current to remote brain areas, such as hippocampus, premotor cortex, and somatosensory cortex.…”

Ventral lateral geniculate input to the medial pons is necessary for visual eyeblink conditioning in rats

“…Sensory stimuli from every modality are sent to the pontine nuclei (PN), which receive projections from the lower brainstem, thalamus, and cerebral cortex (Glickstein et al 1980;Brodal 1981;Mihailoff et al 1989;Schmahmann and Pandya 1989;Wells et al 1989;Knowlton et al 1993;Campolattaro et al 2007). Neurons in the PN project CS information to the cerebellum via mossy fibers in the middle cerebellar peduncle that synapse on granule cells in the cerebellar cortex and on neurons in the interpositus nucleus (Bloedel and Courville 1981;Brodal 1981;Steinmetz and Sengelaub 1992;Mihailoff 1993).…”