Imaging two functional architectures and their interaction in the mouse cerebellar cortex in vivo using the pH sensitive dye neutral red

The para-crystaline or matrix-like uniformity of the cellular ensemble in the cerebellar cortex can be divided into three architectures. These architectures have been described using various experimental methods and include the parasagittal, the transverse, and the patchy mosaic. A major question in the study of cerebellar function is how the two most prominent architectures, the transverse and parasagittal, interact to shape information processing in the cerebellar cortex. Therefore, considerable effort was put forth to evaluate this question using an in vivo mouse preparation combined with optical imaging of the pH sensitive dye neutral red.; It was shown electrical stimulation of the cerebellar cortex in mice generated a transverse optical beam that crossed the entire folium. Our data suggest that the majority of the optical response to surface stimulation of the cerebellum is mediated by activation of post-synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic glutamate receptors but pre-synaptic parallel fibers also contribute. Furthermore, it was shown that blocking inhibitory pathways can influence the intensity of the optical response.; Electrical stimulation of the ipsilateral face or contralateral inferior olive generated parasagittal bands. Our results demonstrated that optical responses evoked by olivary stimulation are mediated by AMPA receptor activation and that the intensity of these responses is modulated by background inhibition.; Our data show that climbing fiber inputs to the cerebellar cortex are suppressed for approximately 100 mum on both sides of an activated parallel fiber beam. The best stimulus parameters for evoking this lateral-inhibition were when olivary stimulation preceded cortical stimulation by 20 ms. This lateral inhibition was also found to be dependent on the activation of gamma aminobutyric acid receptors (GABAA and not GABAB), consistent with a basket cell mediated effect.; Importantly, our data suggest that climbing fiber-evoked responses are not invariant but depend on the state of cortical circuitry. Therefore, theories of cerebellar function need to be modified to incorporate these new data. One hypothesized role for the off-beam inhibition of climbing fiber inputs is to spatially focus the induction of long-term depression to the site of the climbin fiber and parallel fiber interaction.