Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol—consisting of pairing a postsynaptic AP with visually driven presynaptic inputs—modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity.
Nerve cells, called neurons, are one of the core components of the brain and form complex networks by connecting to other neurons via long, thin ‘wire-like’ processes called axons. Axons can extend across the brain, enabling neurons to form connections—or synapses—with thousands of others. It is through these complex networks that incoming information from sensory organs, such as the eye, is propagated through the brain and encoded.
The basic unit of communication between neurons is the action potential, often called a ‘spike’, which propagates along the network of axons and, through a chemical process at synapses, communicates with the postsynaptic neurons that the axon is connected to. These action potentials excite the neuron that they arrive at, and this excitatory process can generate a new action potential that then propagates along the axon to excite additional target neurons. In the visual areas of the cortex, neurons respond with action potentials when they ‘recognize’ a particular feature in a scene—a process called tuning. How a neuron becomes tuned to certain features in the world and not to others is unclear, as are the rules that enable a neuron to change what it is tuned to. What is clear, however, is that to understand this process is to understand the basis of sensory perception.
Memory storage and formation is thought to occur at synapses. The efficiency of signal transmission between neurons can increase or decrease over time, and this process is often referred to as synaptic plasticity. But for these synaptic changes to be transmitted to target neurons, the changes must alter the number of action potentials. Although it has been shown in vitro that the efficiency of synaptic transmission—that is the strength of the synapse—can be altered by changing the order in which the pre- and postsynaptic cells are activated (referred to as ‘Spike-timing-dependent plasticity’), this has never been shown to have an effect on the number of action potentials generated in a single neuron in vivo. It is therefore unknown whether this process is functionally relevant.
Now Pawlak et al. report that spike-timing-dependent plasticity in the visual cortex of anaesthetized rats can change the spiking of neurons in the visual cortex. They used a visual stimulus (a bar flashed up for half a second) to activate a presynaptic cell, and triggered a single action potential in the postsynaptic cell a very short time later. By repeatedly activating the cells in this way, they increased the strength of the synaptic connection between the two neurons. After a small number of these pairing activations, presenting the visual stimulus alone to the presynaptic cell was enough to trigger an action potential (a suprathreshold response) in the postsynaptic neuron—even though this was not the case prior to the pairing.
This study shows that timing rules known to change the strength of synaptic connections—and proposed to underlie learning and memory—have functional relevance in vivo, and that the timing of single action potentials can change the functional status of a cortical neuron.