Behavioral Characteristics, Associative Learning Capabilities, and Dynamic Association Mapping in an Animal Model of Cerebellar Degeneration

Abstract

Porras-García E, Sánchez-Campusano R, Martínez-Vargas D, Domínguez-del-Toro E, Cendelín J, Vožeh F, Delgado-García JM. Behavioral characteristics, associative learning capabilities, and dynamic association mapping in an animal model of cerebellar degeneration. J Neurophysiol 104: 346 -365, 2010. First published April 21, 2010 doi:10.1152/jn.00180.2010. Young adult heterozygous Lurcher mice constitute an excellent model for studying the role of the cerebellar cortex in motor performance-including the acquisition of new motor abilities-because of the early postnatal degeneration of almost all of their Purkinje and granular cells. Wild-type and Lurcher mice were classically conditioned for eyelid responses using a delay paradigm with or without an electrolytic lesion in the interpositus nucleus. Although the late component of electrically evoked blink reflexes was smaller in amplitude and had a longer latency in Lurcher mice than that in controls, the two groups of animals presented similar acquisition curves for eyeblink conditioning. The lesion of the interpositus nucleus affected both groups of animals equally for the generation of reflex and conditioned eyelid responses. Furthermore, we recorded the multiunitary activity at the red and interpositus nuclei during the same type of associative learning. In both nuclei, the neural firing activity lagged the beginning of the conditioned response (determined by orbicularis oculi muscle response). Although red nucleus neurons and muscle activities presented a clear functional coupling (strong correlation and low asymmetry) across conditioning, the coupling between interpositus neurons and either red nucleus neurons or muscle activities was slightly significant (weak correlation and high asymmetry). Lurcher mice presented a nonlinear coupling (high asymmetry) between red nucleus neurons and muscle activities, with an evident compensatory adjustment in the correlation of firing between interpositus and red nuclei neurons (a coupling with low asymmetry), aimed probably at compensating the absence of cerebellar cortical neurons.

Red Nucleus Neurons Actively Contribute to the Acquisition of Classically Conditioned Eyelid Responses in Rabbits

“…The acute disappearance of facilitatory inputs from IP neurons could block these reverberant activities and prevent the learningdepending evolution of rubral activities related to the generation and performance of eyelid CRs. In addition, a reinforcing role of the IP nucleus for the expression of both conditioned and unconditioned eyelid responses has been already shown in recording and/or transient inactivation studies performed in behaving cats (Jiménez-Díaz et al, 2004) and mice (Porras-García et al, 2010). These two phenomena could explain why its inactivation has such a deleterious effects on both conditioned and unconditioned eyelid responses.…”

“…At the same time, RN and pararubral neurons were activated by stimulations of different sensory modalities, suggesting that they could be capable of integrating sensory information with motor commands. Firing rates of these RN and pararubral neurons, during the CS-US interval, seemed to correlate better with the EMG activity of the OO muscle than with the learning curve, suggesting that they were more directly involved in the performance of CRs than in the acquisition process (Desmond and Moore, 1991;Porras-García et al, 2010). The reversible inactivation of the MC during conditioning sessions evoked a significant and lasting reduction in the percentage of CRs and in the firing rates of recorded neurons, with a minor effect on unconditioned responses.…”

Differential Contribution of Hippocampal Circuits to Appetitive and Consummatory Behaviors during Operant Conditioning of Behaving Mice

“…A test that can provide such information is called a "multiple comparison." Multiple comparison procedures were designed to provide an upper bound to the probability that any comparison will incorrectly be found significant (see an application of multiple comparison test in the study by Porras-García et al, 2010). In particular, this procedure was applied for both the means and the peak spectral powers and the corresponding frequency values.…”

Dynamic Changes in the Cerebellar-Interpositus/Red-Nucleus-Motoneuron Pathway During Motor Learning

“…Three different animal paradigms were used: alert behaving cats [11,12] and conscious wild-type and Lurcher mice [18]. As has been shown, Lurcher mice constitute an excellent model for studying the role of the cerebellar cortex in motor performance-including the acquisition of new motor abilities-because of the early postnatal degeneration of almost all of their Purkinje and granular cells [18][19][20][21][22].…”

“…Three different animal paradigms were used: alert behaving cats [11,12] and conscious wild-type and Lurcher mice [18]. As has been shown, Lurcher mice constitute an excellent model for studying the role of the cerebellar cortex in motor performance-including the acquisition of new motor abilities-because of the early postnatal degeneration of almost all of their Purkinje and granular cells [18][19][20][21][22]. The main outcome of this experimental approach is a more complete picture of events taking place simultaneously during the acquisition process, as well as a determination of nonlinear associations and putative temporal and/or causal relationships between recorded variables [23][24][25][26].…”