Distinct mechanisms of spike timing-dependent LTD at vertical and horizontal inputs onto L2/3 pyramidal neurons in mouse barrel cortex

Abstract

Spike timing‐dependent plasticity (STDP) is an attractive candidate to mediate the synaptic changes that support circuit plasticity in sensory cortices during development. STDP is prevalent at excitatory synapses, but it is not known whether the underlying mechanisms are universal, or whether distinct mechanisms underpin STDP at different synapses. Here, we set out to compare and contrast STDP at vertical layer 4 and horizontal layer 2/3 inputs onto postsynaptic layer 2/3 neurons in the mouse barrel cortex. We find that both vertical and horizontal inputs show STDP, but that they display different time windows for induction of timing‐dependent long‐term depression (t‐LTD). Moreover, whereas t‐LTD at vertical inputs requires presynaptic NMDA receptors and is expressed presynaptically, using paired recordings we find that t‐LTD at horizontal inputs requires postsynaptic NMDA receptors and is expressed postsynaptically. These results demonstrate that similar forms of plasticity on the same postsynaptic neuron can be mediated by distinct mechanisms, and suggest that these forms of plasticity may enable these two types of cortical synapses to support different functions.

Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex

“…In all potential connections tested between neurons ( n = 1,056), we found (including connections lost during baseline) a monosynaptic response in 11.0% of cases. Success rate for identified PC–FSIN pairs was 4.0%, PC–non-FSINs connections: 1.9%, PC–PC pairs: 1.1%, and FSIN–PC connections: 3.8%, showing similar or slightly lower connectivity rates than reported in the rodent neocortex L2–3 [21–23]. …”

“…These suggest that there may be various LTD forms in human cortical interneuron synapses [24,25], and that non-FSINs may exhibit different LTD mechanism than the FSINs, possibly depending on postsynaptic depolarization. Indeed, many synapse-specific properties including long-term plasticity have been reported in glutamatergic fibers in the rodent cortex [21,32,47–50]. Correspondingly, synapses originating from the same PC in the human neocortex may exhibit distinct long-term plasticity, depending upon the postsynaptic target cell; and different activity patterns may be required for plasticity in the synapses [24,50].…”

Functional consequences of pre- and postsynaptic expression of synaptic plasticity

“…In the case of short-term plasticity, connections from the same presynaptic neurons onto different cells can short-term depress or facilitate depending on the target cell type [87,88], whereas multiple connections between two neurons are often highly similar [45]. Similarly, while STDP exists at both horizontal and vertical excitatory inputs to visual cortex layer 2/3 pyramidal cells, the mechanistic underpinnings as well as the precise temporal requirements for induction are different [89]. Such specificity suggests that the specific locus of expression of long-term plasticity at a given synapse type is meaningful for the proper functioning of microcircuits in the brain, as otherwise tight regulation of expression locus would not have arisen during the evolution of the brain.…”

Functional consequences of pre- and postsynaptic expression of synaptic plasticity

“…In the case of short-term plasticity, connections from the same presynaptic neurons onto different cells can short-term depress or facilitate depending on the target cell type [87,88], whereas multiple connections between two neurons are often highly similar [45]. Similarly, while STDP exists at both horizontal and vertical excitatory inputs to visual cortex layer 2/3 pyramidal cells, the mechanistic underpinnings as well as the precise temporal requirements for induction are different [89]. Such specificity suggests that the specific locus of expression of long-term plasticity at a given synapse type is meaningful for the proper functioning of microcircuits in the brain, as otherwise tight rstb.royalsocietypublishing.org Phil.…”