bims-climfi Biomed News
on Cerebellar cortical circuitry
Issue of 2019‒05‒12
two papers selected by
Jun Maruta
Mount Sinai Health System

  1. PLoS Comput Biol. 2019 May 06. 15(5): e1006475
    Negrello M, Warnaar P, Romano V, Owens CB, Lindeman S, Iavarone E, Spanke JK, Bosman LWJ, De Zeeuw CI.
      Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor performance and motor learning. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized output. However, the interaction of these properties with torrential synaptic inputs in awake behaving animals is not well understood. Here we combine electrophysiological recordings in awake mice with a realistic tissue-scale computational model of the inferior olive to study the relative impact of intrinsic and extrinsic mechanisms governing its activity. Our data and model suggest that if subthreshold oscillations are present in the awake state, the period of these oscillations will be transient and variable. Accordingly, by using different temporal patterns of sensory stimulation, we found that complex spike rhythmicity was readily evoked but limited to short intervals of no more than a few hundred milliseconds and that the periodicity of this rhythmic activity was not fixed but dynamically related to the synaptic input to the inferior olive as well as to motor output. In contrast, in the long-term, the average olivary spiking activity was not affected by the strength and duration of the sensory stimulation, while the level of gap junctional coupling determined the stiffness of the rhythmic activity in the olivary network during its dynamic response to sensory modulation. Thus, interactions between intrinsic properties and extrinsic inputs can explain the variations of spiking activity of olivary neurons, providing a temporal framework for the creation of both the short-term and long-term changes in cerebellar output.
  2. Front Neural Circuits. 2019 ;13 30
    Dohaku R, Yamaguchi M, Yamamoto N, Shimizu T, Osakada F, Hibi M.
      The cerebellum is involved in some forms of motor coordination and learning, and in cognitive and emotional functions. To elucidate the functions of the cerebellum, it is important to unravel the detailed connections of the cerebellar neurons. Although the cerebellar neural circuit structure is generally conserved among vertebrates, it is not clear whether the cerebellum receives and processes the same or similar information in different vertebrate species. Here, we performed monosynaptic retrograde tracing with recombinant rabies viruses (RV) to identify the afferent connections of the zebrafish cerebellar neurons. We used a G-deleted RV that expressed GFP. The virus was also pseudotyped with EnvA, an envelope protein of avian sarcoma and leucosis virus (ALSV-A). For the specific infection of cerebellar neurons, we expressed the RV glycoprotein (G) gene and the envelope protein TVA, which is the receptor for EnvA, in Purkinje cells (PCs) or granule cells (GCs), using the promoter for aldolase Ca (aldoca) or cerebellin 12 (cbln12), respectively. When the virus infected PCs in the aldoca line, GFP was detected in the PCs' presynaptic neurons, including GCs and neurons in the inferior olivary nuclei (IOs), which send climbing fibers (CFs). These observations validated the RV tracing method in zebrafish. When the virus infected GCs in the cbln12 line, GFP was again detected in their presynaptic neurons, including neurons in the pretectal nuclei, the nucleus lateralis valvulae (NLV), the central gray (CG), the medial octavolateralis nucleus (MON), and the descending octaval nucleus (DON). GFP was not observed in these neurons when the virus infected PCs in the aldoca line. These precerebellar neurons generally agree with those reported for other teleost species and are at least partly conserved with those in mammals. Our results demonstrate that the RV system can be used for connectome analyses in zebrafish, and provide fundamental information about the cerebellar neural circuits, which will be valuable for elucidating the functions of cerebellar neural circuits in zebrafish.
    Keywords:  afferents; cerebellum; connections; granule cells; purkinje cells; rabies virus; zebrafish