A Purkinje cell Timing Mechanism. On the Physical Basis of a Temporal Duration Memory.
type: CreativeWork
description: The standard view of neural signaling is that a neuron can influence its target cell by exciting or inhibiting it. Learning is thought to involve strengthening or weakening synaptic connections. For most behaviors, the brain must learn to produce precisely timed activity patterns. Learned response timing is indispensable for a wide range of tasks and requires learning of interstimulus intervals (ISIs). The learning mechanism thought to accomplish this combines time-varying patterns of activity in the pre-synaptic neural network with changes in synaptic strength between the pre-synaptic neurons active at the end of the ISI and the post-synaptic neuron. 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) …
abstract: The standard view of neural signaling is that a neuron can influence its target cell by exciting or inhibiting it. Learning is thought to involve strengthening or weakening synaptic connections. For most behaviors, the brain must learn to produce precisely timed activity patterns. Learned response timing is indispensable for a wide range of tasks and requires learning of interstimulus intervals (ISIs). The learning mechanism thought to accomplish this combines time-varying patterns of activity in the pre-synaptic neural network with changes in synaptic strength between the pre-synaptic neurons active at the end of the ISI and the post-synaptic neuron. 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) …
author: Johansson, Fredrik
language: eng
keywords: Neurosciences, Cerebellum, Purkinje cell, Timing, Temporal, Memory, Eyeblink conditioning, mGluR7, Kir3, GIRK
date published: 2015
date modified: 2026-07-24T02:59:36Z
provider: University of Lund
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Associative Learning