Cortical feed-forward networks for binding different streams of sensory information

Different streams of sensory information are transmitted to the cortex where they are merged into a percept in a process often termed 'binding.' Using recordings from triplets of rat cortical layer 2/3 and layer 5 pyramidal neurons, we show that specifi

Dendritic mechanisms controlling spike-timing dependent synaptic plasticity

The ability of neurons to modulate the strength of their synaptic connections has been shown to depend on the relative timing of pre- and postsynaptic action potentials. This form of synaptic plasticity, called spike-timing-dependent plasticity (STDP), has become an attractive model for learning at the single-cell level. Yet, despite its popularity in experimental and theoretical neuroscience, the influence of dendritic mechanisms in the induction of STDP has been largely overlooked. Several recent studies have investigated how active dendritic properties and synapse location within the dendritic tree influence STDP. These studies suggest the existence of learning rules that depend on firing mode and subcellular input location, adding unanticipated complexity to STDP. Here, we propose a new look at STDP that is focused on processing at the postsynaptic site in the dendrites, rather than on spike-timing at the cell body

Dendritic Synapse Location and Neocortical Spike-Timing-Dependent Plasticity

While it has been appreciated for decades that synapse location in the dendritic tree has a powerful influence on signal processing in neurons, the role of dendritic synapse location on the induction of long-term synaptic plasticity has only recently been explored. Here, we review recent work revealing how learning rules for spike-timing-dependent plasticity (STDP) in cortical neurons vary with the spatial location of synaptic input. A common principle appears to be that proximal synapses show conventional STDP, whereas distal inputs undergo plasticity according to novel learning rules. One crucial factor determining location-dependent STDP is the backpropagating action potential, which tends to decrease in amplitude and increase in width as it propagates into the dendritic tree of cortical neurons. We discuss additional location-dependent mechanisms as well as the functional implications of heterogeneous learning rules at different dendritic locations for the organization of synaptic inputs

Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 μm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits

Does spike-timing-dependent synaptic plasticity underlie memory formation?

1. Synaptic plasticity is thought to underlie learning and memory formation in the brain. However, how synaptic plasticity is induced during these processes remains controversial. An attractive candidate mechanism for learning at the neuronal level is spike timing-dependent synaptic plasticity (STDP), which depends on the precise (msec) timing of the synaptic input and the post-synaptic action potential. This temporal relationship resembles typical features of associative learning. Here, we review recent evidence suggesting that STDP is likely to underlie certain forms of learning. 2. First, we discuss the cellular mechanisms of STDP elucidated by in vitro experiments. A special focus is put onto aspects known to differ between in vitro preparations and the in vivo situation. 3. Second, we review the experimental induction of STDP in vivo, in various systems ranging from Xenopus tectum to human motor cortex. 4. The last part of the review addresses the question whether STDP can be induced by activity patterns occurring during normal behaviour. 5. We conclude that STDP is a robust phenomenon in vivo and a likely mechanism underlying sensory map plasticity in the neocortex. Further experimental evidence is required to determine whether STDP also has a role in more complex forms of learning

Learning rules for spike timing-dependent plasticity depend on dendritic synapse location

Previous studies focusing on the temporal rules governing changes in synaptic strength during spike timing-dependent synaptic plasticity (STDP) have paid little attention to the fact that synaptic inputs are distributed across complex dendritic trees. During STDP, propagation of action potentials (APs) back to the site of synaptic input is thought to trigger plasticity. However, in pyramidal neurons, backpropagation of single APs is decremental, whereas high-frequency bursts lead to generation of distal dendritic calcium spikes. This raises the question whether STDP learning rules depend on synapse location and firing mode. Here, we investigate this issue at synapses between layer 2/3 and layer 5 pyramidal neurons in somatosensory cortex. We find that low-frequency pairing of single APs at positive times leads to a distance-dependent shift to long-term depression (LTD) at distal inputs. At proximal sites, this LTD could be converted to long-term potentiation (LTP) by dendritic depolarizations suprathreshold for BAC-firing or by high-frequency AP bursts. During AP bursts, we observed a progressive, distance-dependent shift in the timing requirements for induction of LTP and LTD, such that distal synapses display novel timing rules: they potentiate when inputs are activated after burst onset (negative timing) but depress when activated before burst onset (positive timing). These findings could be explained by distance-dependent differences in the underlying dendritic voltage waveforms driving NMDA receptor activation during STDP induction. Our results suggest that synapse location within the dendritic tree is a crucial determinant of STDP, and that synapses undergo plasticity according to local rather than global learning rules

Requirement of dendritic calcium spikes for induction of spike-timing-dependent synaptic plasticity

Spike-timing-dependent synaptic plasticity (STDP) by definition requires the temporal association of pre- and postsynaptic action potentials (APs). Yet, in cortical pyramidal neurons pairing unitary EPSPs with single APs at low frequencies is ineffective at generating plasticity. Using recordings from synaptically coupled layer 5 pyramidal neurons, we show here that high-frequency (200 Hz) postsynaptic AP bursts, rather than single APs, are required for both long-term potentiation (LTP) induction and NMDA channel activation during EPSP–AP pairing at low frequencies. Furthermore, we find that AP bursts can lead to LTP induction and NMDA channel activation during EPSP–AP pairing at both positive and negative times. High-frequency AP bursts generated supralinear calcium signals in basal dendrites suggesting the generation of dendritic calcium spikes, as has been observed previously in apical dendrites during AP burst firing at frequencies greater than 100 Hz. Consistent with a role of these dendritic calcium spikes in LTP induction, pairing EPSPs with low frequency (50 Hz) AP bursts was ineffective in generating LTP. Furthermore, supralinear calcium signals in basal dendrites during AP bursts were blocked by low concentrations of the T- and R-type calcium channel antagonist nickel, which also blocked LTP and NMDA channel activation. These data suggest an important role of dendritic calcium spikes during AP bursts in determining both the efficacy and time window for STDP induction

Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy

Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuit