bims-climfi 2019-05-05 papers

Issue of 2019–05–05
three papers selected by
Jun Maruta, Mount Sinai Health System

Neurobiol Learn Mem. 2019 Apr 24. pii: S1074-7427(19)30078-4. [Epub ahead of print]

Graded error signals in eyeblink conditioning.

Minimizing errors is an important aspect of learning. However, it is not enough merely to record if an error occurred. For efficient learning, information about the magnitude of errors is critical. Did my tennis swing completely miss the target or did I hit the ball, but not quite in the sweet spot? How can neurons - which have traditionally been thought of as binary units - signal the magnitude of an error? Here I review evidence that eyeblink conditioning - a basic form of motor learning - depends on graded signals from the inferior olive which guides plasticity in the cerebellum and ultimately tunes behavior. Specifically, evidence suggests that: (1) Error signals are conveyed to the cerebellum via the inferior olive; (2) Signals from the inferior olive are graded; (3) The strength of the olivary signal affects learning; (4) Cerebellar feedback influences the strength of the olivary signal. I end the review by exploring how graded error signals might explain some behavioral learning phenomena.

Keywords: Cerebellum; Climbing fibers; Error signals; Eyeblink conditioning; Inferior olive; Learning; Nucleo-Olivary pathway; Plasticity; Rescorla-Wagner

DOI: https://doi.org/10.1016/j.nlm.2019.04.011

Nat Neurosci. 2019 Apr 29.

Predictive and reactive reward signals conveyed by climbing fiber inputs to cerebellar Purkinje cells.

Dimitar Kostadinov, Maxime Beau, Marta Blanco Pozo, Michael Häusser.

There is increasing evidence for a cerebellar contribution to cognitive processing, but the specific input pathways conveying this information remain unclear. We probed the role of climbing fiber inputs to Purkinje cells in generating and evaluating predictions about associations between motor actions, sensory stimuli and reward. We trained mice to perform a visuomotor integration task to receive a reward and interleaved cued and random rewards between task trials. Using two-photon calcium imaging and Neuropixels probe recordings of Purkinje cell activity, we show that climbing fibers signal reward expectation, delivery and omission. These signals map onto cerebellar microzones, with reward delivery activating some microzones and suppressing others, and with reward omission activating both reward-activated and reward-suppressed microzones. Moreover, responses to predictable rewards are progressively suppressed during learning. Our findings elucidate a specific input pathway for cerebellar contributions to reward signaling and provide a mechanistic link between cerebellar activity and the creation and evaluation of predictions.

DOI: https://doi.org/10.1038/s41593-019-0381-8

Neurosci Lett. 2019 Apr 25. pii: S0304-3940(19)30293-9. [Epub ahead of print]

Temporal-spacial relationships between facial stimulation-evoked filed potential responses in mouse cerebellar granular layer and molecular layer.

Chang Ma, Di Lu, Li-Xin Cao, Yan-Hua Bing, Chun-Ping Chu, De-Lai Qiu.

The cerebellum receives sensory inputs from mossy fiber-granule cell or climbing fiber pathways, and generates motor-related outputs. However, the temporal and special mechanism of the sensory information processing in cerebellar cortex is still unclear. Therefore, we here investigated the temporal-spacial mechanism between the facial stimulation-evoked field potential responses in granular layer (GL) and molecular layer (ML), by duo-electrophysiological recording technique and pharmacological methods in urethane-anesthetized mice. Our results showed that air-puff stimulation of ipsilateral whisker pad evoked successively field potential responses in GL and ML. The field potential response in GL exhibited a strong excitatory component (N1) followed by an inhibitory component (P1), while the field potential response in ML exhibited a tiny excitatory component (N1) followed by strong inhibitory component (P1). The latency of N1 was decreased with the increase of recording depth in ML, and it was the shortest in GL. Notably, the latencies of P1 in GL and ML were similar regardless the relative recording sites. Furthermore, blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated parallel fiber excitatory inputs by application of AMPA receptor antagonist, NBQX prevented P1 in both ML and GL. Moreover, application of GABAA receptors antagonist, gabazine simultaneously abolished P1 in both ML and GL. These results indicate that the facial stimulation evoked a simultaneous GABAergic inhibition in both ML and GL via mossy fiber-GC-parallel fiber pathway, suggesting that the sensory stimulation simultaneously evoked excitation of molecular layer interneurons (MLIs) and GL Golgi cells in cerebellar cortex.

Keywords: GABA(A) receptor; cerebellar cortical molecular layer; duo-electrophysiological recording; facial stimulation; granule layer; parallel fiber

DOI: https://doi.org/10.1016/j.neulet.2019.04.051