Neurobiol Learn Mem. 2019 Oct 21. pii: S1074-7427(19)30170-4. [Epub ahead of print]
107103
The general consensus for learning and memory, including in the cerebellum, is that modification of synaptic strength via long-term potentiation (LTP) or long-term depression (LTD) are the primary mechanisms for the formation of memories. Recent findings suggest additional cellular mechanisms - referred to as 'intrinsic plasticity' - where a neuron's membrane excitability intrinsically changes. These mechanisms act like a dimmer and alter neuronal responsiveness by adjusting response amplitudes and spike thresholds. Here, I argue that classical conditioning of cerebellar Purkinje cell responses reveals yet another cell-intrinsic learning mechanism which significantly differs from both changes in synaptic strength and changes in membrane excitability. When the conditional (CS) and unconditional stimuli (US) are delivered directly to the Purkinje cell's immediate pre-synaptic afferents, the parallel fibres and the climbing fibre, the cell learns to respond to the CS with a pause in its spontaneous firing that reflects the interval between the two stimuli. The pause response has a delayed onset and adaptively timed maximum, offset and duration, determined by the previously experienced CS-US interval. The timing is not dependent on any network-generated time-varying input. This implies the existence of a timing mechanism and a memory substrate that encodes the duration of the CS-US interval inside the Purkinje cell. Such temporal interval learning is not simply a change that causes more or less firing in response to an input. Here, I review these findings in relation to the standard theory of synaptic strength changes and the network interactions believed to be necessary for generating time codes.
Keywords: Cerebellum; Eyeblink conditioning; Intrinsic plasticity; Purkinje cell; Timing