Download Cerebellar synapses for fear memory

Session: Cellular and network functions of the cerebellum
Fear Conditioning affects Coincidence Detection in Cerebellar
Purkinje Cells
1
Bibiana Scelfo1, Benedetto Sacchetti1, Lan Zhu1 and Piergiorgio Strata1,2
Rita Levi Montalcini Center for Brain Repair, Dept. of Neuroscience, University of Turin
Corso Raffaello 30, Turin, I-10125
2
IRCCS Santa Lucia Foundation -Via Ardeatina 306, Rome, I-00179
[email protected]
Classical fear conditioning is recognized as a model to investigate the neurobiological
mechanisms of learning and memory in the mammalian brain and to understand the root of
fear-related disorders in humans. A growing body of evidence suggests that the cerebellum
is involved in cognitive and emotional functions such as fear (Bernston and Torello 1982;
Schmahmann and Sherman 1998). Recently our group has shown that the neural correlate
of fear memory is provided, in the cerebellar cortex, by a long-term potentiation of the
excitatory synapse between the parallel fibers (PFs) and the Purkinje cell (PC) (Sacchetti et
al., 2004).
Since the axon of the PC is the only output from the cerebellar cortex it is important to
assess if and how fear-induced long term synaptic changes at the PC synapses integrate and
influence its activity. In vivo recordings have shown that classical conditioning can change
the firing patterns of several types of neurons including cerebellar PC (Hesslow and
Iwarsson, 1994).
We performed patch-clamp recordings from rat cerebellar slices in conditioned and naïve
animals with the aim of recording the tonic firing of the PC. We found no difference in the
firing frequency between the two groups as well as in the intrinsic membrane properties
related to excitability of the PC. Thus we went into a more detailed analysis investigating
at a smaller time scale the time window for integration of multiple coincident inputs in the
PC.
Very recently it has been shown in the hippocampus that the temporal fidelity for spike
generation of a neuronal network requires specific levels of excitation and inhibition to be
maintained (Lamsa et al., 2005). Through patch-clamp recordings on coronal slices we
evaluated the probability for PC spike generation as a function of the delay in the
activation of two PF beams. We found that as a response to fear memory PCs able to
integrate excitatory inputs over a wider time window allowing spike generation within a
longer time interval of coincident inputs. This would ensure a more effective detection and
provides evidence that plastic changes located at synaptic level may not affect the basic
firing properties of a neuron but can profoundly influence the neuronal circuit function.
Berntson G.G., Torello M.W. (1982) The paleocerebellum and the integration of behavioral function.
Physiol. Psychol. 0:2-12.
Hesslow G. and Ivarsson M. (1994) Suppression of cerebellar Purkinje cells during conditioned responses in
ferrets. Neuroreport, 5:649-652.
Sacchetti B., Scelfo B., Tempia F., Strata P. (2004) Long-term synaptic changes induced in the cerebellar
cortex by fear conditioning. Neuron, 42:973-982.
Schmahmann, J.D., Sherman, J.C. (1998). The cerebellar cognitive affective syndrome. Brain 121:561-579.
Lamsa K., Heeroma J.H., Kullmann D.M. (2005) Hebbian LTP in feed-forward inhibitory interneurons and
the temporal fidelity of input discrimination. Nat. Neurosci. 8:916-924.