| Research in the cerebellum group led by Professor Yosef Yarom
focuses on the olivo-cerebellar system. Cerebellar function, which was
classically thought to be restricted to motor-coordination, has
recently been extended to include both sensory and cognitive functions.
The simplicity and homogeneity of the circuitry of this modular
structure suggest it has a rather limited repertoire of functional
capabilities. More crucially, the multiplicity of functions and the
simplicity of the circuit imply that this system reflects a very basic
computational process that can be implemented in a variety of brain
functions. One such basic process is the ability to generate precise
time sequences. In fact, many cerebellar-related behaviors involve the
need for precise timing to coordinate different facets of overall
behavior. Recent findings on the functional organization of the
cerebellar cortex, the inferior olivary nucleus, and their
interconnections have prompted us to formulate a hypothetical mechanism
by which the system can generate complex temporal patterns (Yarom
& Cohen 2002). The working hypothesis is that temporal patterns
are encoded in the complex-spike trains that are evoked in a
specifically designlibsane-abatoned designed olivary network that
generates propagating subthreshold oscillations (Devor & Yarom,
2002). This mechanism is presented in Figure 1. The network, which is
tailored to a specific pattern, is defined by bi-stable Purkinje cell
activity (Loewenstein et al., 2005) via the descending inhibitory
connections from the deep cerebellar nuclei to the inferior olive. By
dynamically modulating the electrical connections, this inhibitory path
shapes the functional architecture of the olivary network. Once a
network of olivary neurons is configured, it will generate subthreshold
oscillations that propagate along the network. Olivary action
potentials, which are elicited at the peaks of the propagating wave of
oscillations (Lampl & Yarom, 1993; Chorev et al., 2007),
converge, with various phase relations, onto the neurons of the deep
cerebellar nuclei. Hence, a specific temporal pattern can be generated
in the DCN, and is not bound by the fundamental frequency of the
subthreshold oscillations. This hypothesis posits that input to the
cerebellum, which is actually a call for a specific temporal pattern,
will switch a group of Purkinje cells to an up-state of prolonged
firing/spike discharge. This will form a specific functional network of
olivary neurons. The resultant wave of oscillations will generate the
required temporal pattern. Since the specificity of the recalled
pattern is determined by a group of Purkinje cells activated by mossy
fiber input via the parallel fiber system, we believe that learning of
a specific pattern must occur at the granule cell – Purkinje cell
synapse, in accordance with most theories of cerebellar learning. In
the laboratory we use in vivo and in vitro approaches, combined with
intra- and extracellular recordings as well as imaging of voltage
sensitive dyes to explore various aspects of this hypothetical
mechanism. |
Chorev E, Yarom Y
& Lampl I.
(2007). Rhythmic episodes of subthreshold membrane potential
oscillations in the rat inferior olive nuclei in vivo. J Neurosci 27,
5043-5052.
Devor A & Yarom Y. (2002). Generation and
Propagation of Subthreshold Waves in a Network of Inferior Olivary
Neurons. Journal of neurophysiology 87, 3059-3069.
Lampl I
& Yarom Y. (1993). Subthreshold oscillations of the membrane
potential: a functional synchronizing and timing device. Journal of
neurophysiology 70, 2181-2186.
Loewenstein Y, Mahon S,
Chadderton P, Kitamura K, Sompolinsky H, Yarom Y & Hausser M.
(2005). Bistability of cerebellar Purkinje cells modulated by sensory
stimulation. Nature neuroscience 8, 202-211. |
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