Biomedical subjects

Per Jesper Sjöström

Publications and source records attributed to Per Jesper Sjöström.

10 recordsLinked to original sources

PubMed2006

Optimal information storage in noisy synapses under resource constraints.

Experimental investigations have revealed that synapses possess interesting and, in some cases, unexpected properties. We propose a theoretical framework that accounts for three of these properties: typical central synapses are noisy, the distribution of synaptic weights among central synapses is wide, and synaptic connectivity between neurons is sparse. We also comment on the possibility that synaptic weights may vary in discrete steps. Our approach is based on maximizing information storage capacity of neural tissue under resource constraints. Based on previous experimental and theoretical work, we use volume as a limited resource and utilize the empirical relationship between volume and synaptic weight. Solutions of our constrained optimization problems are not only consistent with existing experimental measurements but also make nontrivial predictions.

Animals↗

PubMed2006

Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses.

Long-term potentiation and depression (LTP and LTD) are cellular plasticity phenomena expressed at a variety of central synapses, and are thought to contribute to learning and developmental changes in circuitry. Recurrent neocortical layer-5 synapses are thought to express a presynaptic form of LTP that influences the short-term plasticity of the synapse. Here we show that changes in synaptic strength elicited by pairing high frequency pre- and postsynaptic firing at this synapse result from a mixture of presynaptic and postsynaptic forms of plasticity, as assessed by the analysis of changes in coefficient of variation, short-term plasticity, and NMDA:AMPA current ratios. Pharmacological dissection of this plasticity revealed that block of presynaptic LTD with an endocannabinoid inhibitor enhanced LTP, while the apparently presynaptic component of LTP could be prevented by induction in the presence of blockers of nitric oxide. These data suggest that correlated high-frequency firing at layer-5 synapses simultaneously induces a mixture of presynaptic LTD, presynaptic LTP, and postsynaptic LTP.

Animals↗

PubMed2006

A cooperative switch determines the sign of synaptic plasticity in distal dendrites of neocortical pyramidal neurons.

Pyramidal neurons in the cerebral cortex span multiple cortical layers. How the excitable properties of pyramidal neuron dendrites allow these neurons to both integrate activity and store associations between different layers is not well understood, but is thought to rely in part on dendritic backpropagation of action potentials. Here we demonstrate that the sign of synaptic plasticity in neocortical pyramidal neurons is regulated by the spread of the backpropagating action potential to the synapse. This creates a progressive gradient between LTP and LTD as the distance of the synaptic contacts from the soma increases. At distal synapses, cooperative synaptic input or dendritic depolarization can switch plasticity between LTD and LTP by boosting backpropagation of action potentials. This activity-dependent switch provides a mechanism for associative learning across different neocortical layers that process distinct types of information.

Animals↗

PubMed2006

Novel presynaptic mechanisms for coincidence detection in synaptic plasticity.

Long-term plasticity typically relies on postsynaptic NMDA receptors to detect the coincidence of pre- and postsynaptic activity. Recent studies, however, have revealed forms of plasticity that depend on coincidence detection by presynaptic NMDA receptors. In the amygdala, cortical afferent associative presynaptic long-term potentiation (LTP) requires activation of presynaptic NMDA receptors by simultaneous thalamic and cortical afferents. Surprisingly, both types of afferent can also undergo postsynaptically induced NMDA-receptor-dependent LTP. In the neocortex, spike-timing-dependent long-term depression (LTD) requires simultaneous activation of presynaptic NMDA autoreceptors and retrograde signalling by endocannabinoids. In cerebellar LTD, presynaptic NMDA receptor activation suggests that similar presynaptic mechanisms may exist. Recent studies also indicate the existence of presynaptic coincidence detection that is independent of NMDA receptors, suggesting that such mechanisms have a widespread role in plasticity.

Action Potentials↗

PubMed2005

Highly nonrandom features of synaptic connectivity in local cortical circuits.

How different is local cortical circuitry from a random network? To answer this question, we probed synaptic connections with several hundred simultaneous quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual cortex. Analysis of this dataset revealed several nonrandom features in synaptic connectivity. We confirmed previous reports that bidirectional connections are more common than expected in a random network. We found that several highly clustered three-neuron connectivity patterns are overrepresented, suggesting that connections tend to cluster together. We also analyzed synaptic connection strength as defined by the peak excitatory postsynaptic potential amplitude. We found that the distribution of synaptic connection strength differs significantly from the Poisson distribution and can be fitted by a lognormal distribution. Such a distribution has a heavier tail and implies that synaptic weight is concentrated among few synaptic connections. In addition, the strengths of synaptic connections sharing pre- or postsynaptic neurons are correlated, implying that strong connections are even more clustered than the weak ones. Therefore, the local cortical network structure can be viewed as a skeleton of stronger connections in a sea of weaker ones. Such a skeleton is likely to play an important role in network dynamics and should be investigated further.

Animals↗

PubMed2004

Endocannabinoid-dependent neocortical layer-5 LTD in the absence of postsynaptic spiking.

Long-term depression (LTD) was induced in neocortical layer 5 pyramidal connections by pairing presynaptic firing with subthreshold postsynaptic depolarization (dLTD) or via a spike-timing protocol (tLTD). Like tLTD, dLTD reduced short-term depression and increased the coefficient of variation consistent with a presynaptic site of expression. Also like tLTD, dLTD was blocked by CB1 cannibinoid receptor blockade and required activation of presumably presynaptic NR2B-containing N-methyl-D-aspartate receptors. The two forms of LTD had identical magnitudes and time courses and occluded one another, and neither depended on frequency. Finally, dLTD shares with tLTD the asymmetric temporal window of induction. In conclusion, the types of LTD induced by these two protocols are indistinguishable, suggesting that the mechanism that underlies tLTD paradoxically does not require postsynaptic spiking: The subthreshold postsynaptic depolarizations of dLTD appear to fully substitute for postsynaptic spiking.

Action Potentials↗

PubMed2004

A proportional but slower NMDA potentiation follows AMPA potentiation in LTP.

Most excitatory glutamatergic synapses contain both AMPA and NMDA receptors, but whether these receptors are regulated together or independently during synaptic plasticity has been controversial. Although long-term potentiation (LTP) is thought to selectively enhance AMPA currents and alter the NMDA-to-AMPA ratio, this ratio is well conserved across synapses onto the same neuron. This suggests that the NMDA-to-AMPA ratio is only transiently perturbed by LTP. To test this, we induced LTP at rat neocortical synapses and recorded mixed AMPA-NMDA currents. We observed rapid LTP of AMPA currents, as well as delayed potentiation of NMDA currents that required previous AMPA potentiation. The delayed potentiation of NMDA currents restored the original NMDA-to-AMPA ratio within 2 h of LTP induction. These data suggest that recruitment of AMPA receptors to synapses eventually induces a proportional increase in NMDA current. This may ensure that LTP does not alter the relative contributions of these two receptors to synaptic transmission and information processing.

Animals↗

PubMed2003

Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors.

There is a consensus that NMDA receptors (NMDARs) detect coincident pre- and postsynaptic activity during induction of long-term potentiation (LTP), but their role in timing-dependent long-term depression (tLTD) is unclear. We examine tLTD in neocortical layer 5 (L5) pyramidal pairs and find that tLTD is expressed presynaptically, implying retrograde signaling. CB1 agonists produce depression that mimics and occludes tLTD. This agonist-induced LTD requires presynaptic activity and NMDAR activation, but not postsynaptic Ca(2+) influx. Further experiments demonstrate the existence of presynaptic NMDARs that underlie the presynaptic activity dependence. Finally, manipulating cannabinoid breakdown alters the temporal window for tLTD. In conclusion, tLTD requires simultaneous activation of presynaptic NMDA and CB1 receptors. This novel form of coincidence detection may explain the temporal window of tLTD and may also impart synapse specificity to cannabinoid retrograde signaling.

Animals↗

PubMed2002

Rate and timing in cortical synaptic plasticity.

Debate has raged over the past few years as to whether cortical neurons transmit information primarily in their average firing rates or in the precise timing of their spikes. Here, we address the related question of which features of spike trains control plasticity at cortical synapses. Using paired recording in slices we have developed a quantitative and predictive description of the joint dependence of cortical plasticity on the rate and relative timing of pre- and postsynaptic firing. The results hold important implications for which parts of the neural code are most readily stored for later retrieval.

Action Potentials↗

PubMed2002

Spike timing, calcium signals and synaptic plasticity.

Plasticity at central synapses depends critically on the timing of presynaptic and postsynaptic action potentials. Key initial steps in synaptic plasticity involve the back-propagation of action potentials into the dendritic tree and calcium influx that depends nonlinearly on the action potential and synaptic input. These initial steps are now better understood. In addition, recent studies of processes as diverse as gene expression and channel inactivation suggest that responses to calcium transients depend not only their amplitude, but on their time course and on the location of their origin.

Action Potentials↗