Short-Term Facilitation of Long-Range Corticocortical Synapses Revealed by Selective Optical Stimulation

Abstract

Short-term plasticity regulates the strength of central synapses as a function of previous activity. In the neocortex, direct synaptic interactions between areas play a central role in cognitive function, but the activity-dependent regulation of these long-range corticocortical connections and their impact on a postsynaptic target neuron is unclear. Here, we use an optogenetic strategy to study the connections between mouse primary somatosensory and motor cortex. We found that short-term facilitation was strong in both corticocortical synapses, resulting in far more sustained responses than local intracortical and thalamocortical connections. A major difference between pathways was that the synaptic strength and magnitude of facilitation were distinct for individual excitatory cells located across all cortical layers and specific subtypes of GABAergic neurons. Facilitation was dependent on the presynaptic calcium sensor synaptotagmin-7 and altered by several optogenetic approaches. Current-clamp recordings revealed that during repetitive activation, the short-term dynamics of corticocortical synapses enhanced the excitability of layer 2/3 pyramidal neurons, increasing the probability of spiking with activity. Furthermore, the properties of the connections linking primary with secondary somatosensory cortex resemble those between somatosensory–motor areas. These short-term changes in transmission properties suggest long-range corticocortical synapses are specialized for conveying information over relatively extended periods.

State-dependent modulation of activity in distinct layer 6 corticothalamic neurons in barrel cortex of awake mice

“…Such precisely timed changes in CT cell activity before self-generated whisker movement could provide context-dependent control of information processing in somatosensory thalamocortical circuits during active sensation (Lee et al, 2008). Indeed, previous studies in rodents have shown that L6 wS1 neurons receive excitatory input from the whisker primary motor cortex (Zhang and Deschenes, 1998; Lee et al, 2008; Rocco-Donovan et al, 2011; Kinnischtzke et al, 2014; Kinnischtzke et al, 2016; Martinetti et al, 2022), a cortical area that appears to contribute to the initiation and modulation of whisking (Carvell et al, 1996; Sreenivasan et al, 2016). The enhancing and suppressive effects of such motor-preparatory signals on CT firing most likely depend on the engagement of specific excitatory and inhibitory mechanisms in L6 (Beierlein and Connors, 2002; Crandall et al, 2017; Frandolig et al, 2019; Martinetti et al, 2022).…”

State-Dependent Modulation of Activity in Distinct Layer 6 Corticothalamic Neurons in Barrel Cortex of Awake Mice

“…Stereotactic Injections. For some mice (n = 2), an adeno-associated virus (AAV) that encoded Cre-dependent genes for hChR2(H134R)-EYFP fusion proteins was injected into the right wS1 during the head-posting procedure, as previously described (Crandall et al, 2015;Martinetti et al, 2022) (pAAV1.Ef1a.DIO.hChRr2(H134R)-eYFP.WPRE.hGH, Addgene: 20298-AAV1). Briefly, after the craniotomy was made over wS1, a small volume of the virus was then pressure-ejected via a glass micropipette attached to a Picospritzer pressure system (0.33 µl over 10-15 min; titer = ~3.4 x 10 12 viral genomes/ml).…”

“…Histology and Imaging. All tissue for histology was prepared from acute brain slices, as previously described (Crandall et al, 2017;Martinetti et al, 2022). Briefly, animals were anesthetized with isoflurane before being decapitated.…”

“…Indeed, previous studies in rodents have shown that L6 wS1 neurons receive excitatory input from the whisker primary motor cortex (Zhang and Deschenes, 1998;Lee et al, 2008;Rocco-Donovan et al, 2011;Kinnischtzke et al, 2014;Kinnischtzke et al, 2016;Martinetti et al, 2022), a cortical area that appears to contribute to the initiation and modulation of whisking (Carvell et al, 1996;Sreenivasan et al, 2016). The enhancing and suppressive effects of such motorpreparatory signals on CT firing most likely depend on the engagement of specific excitatory and inhibitory mechanisms in L6 (Beierlein and Connors, 2002;Crandall et al, 2017;Frandolig et al, 2019;Martinetti et al, 2022).…”

Somatostatin and Somatostatin-Containing Interneurons—From Plasticity to Pathology

“…Moreover, it interfered with the long-range synchrony of neuronal activations between mPFC and hippocampus, indicating that SOM-INs may facilitate long-range synchrony. Recent results revealed that the long-range intracortical inputs to SOM-INs are weak [ 89 , 90 ]. However, VIP-INs are strongly activated and, as they project to SOM-INs, a disinhibitory effect, causing activation of pyramidal neurons, was observed [ 89 ].…”