The Role of Temporal Memory in Cerebellar Purkinje Cells for Motor Timing, by Fredrik Johansson

Summary

The general consensus for learning and memory is that changes in synaptic strength via long-term potentiation (LTP) and long-term depression (LTD) are the primary mechanisms for the formation of memories. Here, I will make the case that cerebellar Purkinje cell responses during eyeblink conditioning paradigms reveal a previously unknown cell-intrinsic learning mechanism which significantly differs from both LTP/LTD 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 temporally separated CS and US onsets. After training, the CS duration can be manipulated but the cell still responds with the duration, e.g. 200 ms, that it was previously trained to.

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 itself. Such temporal interval learning is not simply a change that causes more or less firing in response to an input. Instead, the Purkinje cell appears to learn an adaptively delayed interruption of the cell’s spontaneous firing for a specific duration.

Key papers for the talk:

• Johansson, F., Jirenhed, D. A., Rasmussen, A., Zucca, R., & Hesslow, G. (2014). Memory

trace and timing mechanism localized to cerebellar Purkinje cells. PNAS, 111

• Johansson, F., Hesslow, G., & Medina, J. F. (2016). Mechanisms for motor timing in

the cerebellar cortex. Curr Opin Behav Sci, 8

Short Biography:

I studied medicine and received my Ph.D. in neuroscience from Lund University in Sweden where I have now worked 10 years studying cerebellar physiology in vivo, mostly with Prof. Germund Hesslow. For the last 3 years I have also been a visiting research fellow at University College London studying Purkinje cell learning mechanisms in vitro with Prof. Andrew Batchelor and Prof. Christopher Yeo.

My investigations have mostly focused on associative learning using the eyeblink conditioning paradigm in a de-cerebrate mammal preparation which provides some unique advantages over more commonly used experimental preparations. This allows long and stable recordings from Purkinje cells during the entire cycle of acquisition and extinction as well as pharmacological manipulation of learned motor responses, without the influence of forebrain inputs to the cerebellum and without the influence of anesthesia on the cerebellar circuits. This in combination with our capability of identifying which Purkinje cells in each given animal control a given muscle has led to a long and consistent step-by-step line of research that will be presented during the seminar.

More information on F. Johansson’s web page