A Purkinje cell Timing Mechanism. On the Physical Basis of a Temporal Duration Memory.
Author
Summary, in English
Timing-dependent learning can be studied in eyeblink conditioning. If a neutral conditional stimulus is paired with an unconditional blink-eliciting stimulus, at an ISI of fixed duration, it acquires the ability to elicit a blink that peaks near the end of the ISI. Cerebellar Purkinje cells that control the blink acquire adaptively timed pauses in spontaneous firing, conditioned Purkinje cell responses, that interrupt their tonic inhibition of cerebellar nuclear cells and cause excitatory output that generates the overt blink.
Most models assume the generation of a time code instantiated in varying patterns of activity in the presynaptic granule cells that represent the passage of time. However, we show here (paper I) that a cerebellar Purkinje cell can learn to respond to a specific input with adaptively timed pauses without such a temporally patterned input. Training Purkinje cells with direct stimulation of their presynaptic fibers, and pharmacological blocking of interneurons shows that the timing mechanism is intrinsic to the cell itself and not an emergent property of the network.
That an individual neuron can learn temporal relationships suggests the existence of intracellular temporal duration memory. We demonstrate that this Purkinje cell memory is triggered by the metabotropic glutamate receptor 7 (paper II) and that the timed voltage response in large part is produced by the G-protein activated K+ channel family Kir3/GIRK (paper III). The implication is that a learned and adjustable timing of a metabotropic signaling cascade constitutes a physical memory of temporal duration. A theoretical model (paper IV) describes how this could be accomplished by a learning mechanism that selects among a finite number of regulatory proteins, those which bestow the intracellular signaling cascade with latencies to activation and deactivation that matches the ISI.
The results presented in this thesis show that the traditional view of learning as a change in synaptic strength is insufficient. Finally, because Purkinje cells directly control the conditioned eyeblink we believe that, to our knowledge, this is the first time that a causal link can be shown between a learned and timing-dependent behavior and not only a single neuron’s memory, but also the specific activating receptor of said memory and the specific ion channel that puts it into effect.
Department/s
Publishing year
2015
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2015:75
Full text
- Available as PDF - 14 MB
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Document type
Dissertation
Publisher
Associative Learning
Topic
- Neurosciences
Keywords
- Cerebellum
- Purkinje cell
- Timing
- Temporal
- Memory
- Eyeblink conditioning
- mGluR7
- Kir3
- GIRK
Status
Published
Research group
- Associative Learning
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-154-5
Defence date
13 June 2015
Defence time
10:00
Defence place
Segerfalksalen, BMC A10, Sölvegatan 17, Lund
Opponent
- Clémént Léna