Abstract
Information transfer between principal neurons in neocortex occurs through (glutamatergic) synaptic transmission. In this focussed review, we provide a detailed overview on the strength of synaptic neurotransmission between pairs of excitatory neurons in human and laboratory animals with a specific focus on data obtained using patch clamp electrophysiology. We reach two major conclusions: (1) the synaptic strength, measured as unitary excitatory postsynaptic potential (or uEPSP), is remarkably consistent across species, cortical regions, layers and/or cell-types (median 0.5 mV, interquartile range 0.4–1.0 mV) with most variability associated with the cell-type specific connection studied (min 0.1–max 1.4 mV), (2) synaptic function cannot be generalized across human and rodent, which we exemplify by discussing the differences in anatomical and functional properties of pyramidal-to-pyramidal connections within human and rodent cortical layers 2 and 3. With only a handful of studies available on synaptic transmission in human, it is obvious that much remains unknown to date. Uncovering the shared and divergent principles of synaptic transmission across species however, will almost certainly be a pivotal step toward understanding human cognitive ability and brain function in health and disease.
Excitatory (glutamatergic) synaptic transmission is the primary mode of communication between principal neurons in the neocortex and allows information transfer between synaptically connected neurons. Local inhibitory (GABAergic) synapses modulate (i.e., reduce or disinhibit) the activity of neighboring principal neurons but do not directly contribute to information transfer, at least in the adult (Rheims et al., 2008; Kirmse et al., 2015). The basic blueprint of the synapse typically includes the neurotransmitter release machinery of the presynaptic axon and the associated receptor complex on the postsynaptic dendrite. However, this simplified scheme is easily extended to a spectrum of synapse types, including (i) axo-axonic synapses (Somogyi, 1977; ; Schneider-Mizell et al., 2021), (ii) axo-somatic synapses (; Kubota et al., 2016), (iii) dendro-dendritic synapses [(Woolf et al., 1991; )], or (iii) the tripartite synapse with juxta-posed astrocytes [(; Liu et al., 2023)]. Furthermore, a single postsynaptic spine can be occupied by multiple presynaptic terminals and contact points are found between axonal bouton and postsynaptic spine neck or dendritic shaft (). Because the synapse is the fundamental locus for communication between neurons, it is not surprising that synaptic dysfunction leads to a plethora of brain disorders.
Structural features of individual synapses are studied at maximal spatial resolution using electron microscopy (EM), which can also provide information on the parent neuronal cell type and the local microcircuit (Kasthuri et al., 2015; Schmidt et al., 2017; Loomba et al., 2022). EM typically provides quantitative insight into absolute synapse number or synapse density, which in turn are specific to the brain region or sub-region (e.g., cortical layer) under investigation (). Single dendrite or single spine analysis using EM further uncovered branch-specific spine densities which can be extrapolated to a cumulative number of total spines per neuron (; ). This total number of synapses per neuron is an estimate of the total number of excitatory inputs that an identified postsynaptic neuron may receive (10,000–30,000), which ultimately determines the complexity of input/output transformations. Studies focusing on synapse structure have shown that, in cortical microcircuits, spine shape (; Ofer et al., 2022), spine density (, ; Loomba et al., 2022), or total number of spines per neuron can be highly divergent between species. For example, the number of presynaptic vesicles is higher in humans compared to rodents (Yakoubi et al., 2019a,b), and postsynaptic densities are larger ().
Dense (and/or saturated) reconstruction methods using EM have advanced the field of neuroanatomy by revealing not only synapse structure and local connectivity, but also by uncovering the wiring rules of local microcircuits across highly diverse brain regions for rapidly increasing volumes (; Kasthuri et al., 2015; Motta et al., 2019; Shapson-Coe et al., 2021). However, the functional characterization of synaptic transmission remains necessary, to translate static snapshots of wiring principles into dynamic properties of information transfer. These types of experiments are typically performed by dual recordings of synaptically connected neurons (Qi et al., 2020). Synchronous recording of multiple neurons increases the mapping efficiency but is technically demanding (Lefort et al., 2009; Perin et al., 2011; ; Seeman et al., 2018; Peng et al., 2019; ). This approach also complicates a precise reconstruction of axonal morphology of pre- and postsynaptic neurons due to the extensive overlap of thin axons with relatively large somatodendritic domains. Wiring diagrams have been mapped with particular focus on sensory cortices (Lefort et al., 2009; ; ; Markram et al., 2015; ). These efforts reveal a complex interplay between morphologically identified cell types, connectivity rates and synapse function (; Lefort et al., 2009; ). With the advent of new technologies to define cell types by their transcriptomic profile (; Scala et al., 2019; ), it remains crucial to use a consistent and unambiguous procedure to identify neuronal cell types as part of the experimental design. This is particularly important in view of wiring diagrams in which neurons have a variety of postsynaptic partners, and presynaptic neurons tuning their synaptic properties to the cell-type specific identity of the post-synaptic target neuron (Lefort et al., 2009; Peng et al., 2019). In addition, pre-synaptic neurotransmitter release, mean PSP amplitude, short-term depression or facilitation, and recovery from synaptic depression can be highly specific for the connection under study (). In short, with only a fraction of all possible cell-to-cell connections characterized in any species, it is too early to generalize synaptic function for highly heterogeneous populations of neuronal cell types.
Fundamental properties of synaptic function include synaptic strength (excitatory/inhibitory postsynaptic potential or EPSP/IPSP, in mV, Figure 1 and Table 1), the dynamics during repetitive stimulation (facilitation/depression, paired pulse ratio), EPSP/IPSP decay kinetics (in ms), ionotropic receptor composition at the postsynaptic membrane, recovery from synaptic depression (τ, in ms) or long-term plasticity (LTP/LTD) rules. We are only beginning to understand how synaptic transmission may vary across species. In this focused review, we aim to summarize recent data on (excitatory) synaptic transmission in rodent and human cortical microcircuits. We compile data on unitary synaptic connections that have been mapped using whole-cell patch clamp electrophysiology. Most of this data comes from synaptic connections between pairs of pyramidal cells in layers 2/3 in which subtypes of pyramidal cells are typically pooled (Figure 1 and Table 1). We also include information on additional cortical layers, and where possible, provide information on specific pre- and postsynaptic cell type (i.e., L4 spiny stellate vs. L4 star pyramid or L6 corticocortical vs. L6 corticothalamic pyramidal cell, Figure 1 and Table 2). Note that in the majority of these connectivity studies, by convention, an extracellular calcium concentration of 2 mM (∼1.7 mM free Ca2+) was used; only a small subset used a calcium concentration of 1.3 mM with a minority of studies using concentrations of 1.8 mM, 2.5 mM, or 3.0 mM.
FIGURE 1
TABLE 1
| References | Region | Age | Connection ID | Temp. (°C) | (Ca2+)o (mM) | Stats | Amplitude (mV) |
| Human neocortex | adult | L3-L2 | 31–33 | 1.3 | median | 0.18 | |
| Mouse V1 | PN22-26 | L2/3-L2/3 | 28 | 2 | median | 0.19 | |
| Seeman et al., 2018 | Mouse V1 | PN46.7 ± 6.4 | L2/3-L2/3 | 31–33 | 1.3 | median | 0.26 |
| Mouse V1 | >2 months | L2/3-L2/3 | 2 | average | 0.34 | ||
| Lefort et al., 2009 | Mouse S1 | PN18-21 | L2-L3 | 35 | 2 | median | 0.35 |
| Human neocortex | adult | L2-L2 | 31–33 | 1.3 | median | 0.37 | |
| Human neocortex | adult | L3-L3 | 31–33 | 1.3 | median | 0.37 | |
| Mouse TeA | adult | L2/L3-L2/L3 | 34 | 2 | median | 0.38 | |
| Luo et al., 2017 | Mouse TeA | PN14-21 | L2MN-L2RS | 34–35 | 2 | median | 0.42 |
| Mouse S1 | PN22 ± 0.2 | L2-L2 | 37 | 1.8 | average | 0.43 | |
| Rat V1 | PN19-27 | L2/3 | 23-26 or 36 | 2 | average | 0.43 | |
| Povysheva et al., 2006 | macaca PFC | young adult | L2/3-L2/3 | 31–32 | 2 | average | 0.45 |
| Rat V1/S1 | PN14-16 | L2/3-L2/3 | 32–34 | 2 | median | 0.46 | |
| Lefort et al., 2009 | Mouse S1 | PN18-21 | L2-L2 | 35 | 2 | median | 0.46 |
| Lefort et al., 2009 | Mouse S1 | PN18-21 | L3-L3 | 35 | 2 | median | 0.48 |
| Human neocortex | adult | L2-L3 | 31–33 | 1.3 | median | 0.48 | |
| Povysheva et al., 2006 | Rat PFC | PN19-29 | L2/3-L2/3 | 31–32 | 2 | average | 0.52 |
| Lefort et al., 2009 | Mouse S1 | PN18-21 | L3-L2 | 35 | 2 | median | 0.59 |
| Rat visual cortex | PN20-22 | L2/3 | 36 | 2.5 | average | 0.62 | |
| Luo et al., 2017 | Mouse TeA | PN14-21 | L2RS-L2MN | 34–35 | 2 | median | 0.81 |
| Rat S1 | PN17-23 | L2/3-L2/3 | 34–36 | 2 | median | 0.83 | |
| Luo et al., 2017 | Mouse TeA | PN14-21 | pooled | 34–35 | 2 | median | 0.91 |
| Koester and Johnston, 2005 | Rat S1 | PN12-16 | L2/3 | 35 | 2 | average | 0.92 |
| Luo et al., 2017 | Mouse TeA | PN14-21 | L2MN-L2MN | 34–35 | 2 | median | 0.97 |
| Human MTG | adult | L2/L3-L2/L3 | 34 | 2 | median | 1.12 | |
| Komlosi et al., 2012 | Human PFC | male 48 ± 16 years female 53 ± 17 years | L2/L3-L2/L3 | 36 | 2 | average | 1.56 |
| Szegedi et al., 2016 | Human frontal, temp., parietal | 10–85 years | L2/L3-L2/L3 | 36–37 | 3 | average | 2.01 |
uEPSP amplitude (in mV) for excitatory, pyramidal-to-pyramidal connections in cortical layer 2/3 across species.
TABLE 2
| References | Region | Age | Connection ID | Temp. (°C) | [Ca2+]o (mM) | Stats | Amplitude (mV) |
| Yang et al., 2021b | Rat S1 | PN17-21 | pre L6A CT PN | 30–33 | 2 | average | 0.09 |
| Seeman et al., 2018 | Mouse V1 | PN46.7 ± 6.4 | Tlx3 | 31–33 | 1.3 | median | 0.14 |
| Qi and Feldmeyer, 2016 | Rat S1 | PN18-28 | L4 SSC-L6A | 32–33 | 2 | average | 0.29 |
| Seeman et al., 2018 | Mouse V1 | PN46.7 ± 6.4 | Rorb | 31–33 | 1.3 | median | 0.31 |
| Qi and Feldmeyer, 2016 | Rat S1 | PN18-28 | L4 SPN-L6A | 32–33 | 2 | average | 0.31 |
| Seeman et al., 2018 | Mouse V1 | PN46.7 ± 6.4 | Sim1 | 31–33 | 1.3 | median | 0.33 |
| Yang et al., 2021b | Rat S1 | PN17-21 | pre L6A CC PN | 30–33 | 2 | average | 0.37 |
| Rollenhagen et al., 2018 | Rat S1 | PN30-35 | L5B-L5B | 34–37 | 2 | average | 0.39 |
| All L2/3 | Mixed | Mixed | All L2/3 | Mixed | Mixed | 0.46 | |
| Rat S1 | PN17-23 | L4-L5A | 34-36 | 2 | median | 0.48 | |
| Rat S1 | PN17-23 | L4-L2/3 | 34–36 | 2 | median | 0.5 | |
| Rat S1 | PN24-29 | L5A-L5A | 33–36 | 2 | average | 0.65 | |
| Yang et al., 2021b | Rat S1 | PN17-21 | pre L6A CCla PN | 30–33 | 2 | average | 0.7 |
| Song et al., 2005 | Rat V1 | PN12-20 | L5tt-L5tt | 32–34 | 2.5 | average | 0.77 |
| Reyes and Sakmann, 1999 | Rat sensorimotor cortex | PN14 | L5tt-L5tt | 34 | 2 | average | 1.0 |
| Rat S1 | PN12-15 | L4 SSC-L4 SPN | 36 | 2 | median | 1.02 | |
| Rat S1 | PN14-16 | L5A-L5A | 33-36 | 2 | average | 1.1 | |
| Rat S1 | PN12-15 | L4 SSC-L4 SSC | 36 | 2 | median | 1.19 | |
| Rat S1 | PN18-20 | L5A-L5A | 32–35 | 2 | average | 1.2 | |
| Markram et al., 1997 | Rat S1 | PN14-16 | L5tt-L5tt | 32–34 | 2 | average | 1.3 |
| Rat S1 | PN12-15 | L4 SPN-L4 SSC | 36 | 2 | median | 1.32 | |
| Rat S1 | PN12-15 | L4 SPN-L4 SPN | 36 | 2 | median | 1.38 | |
| Qi et al., 2017 | Rat S1 | PN17-33 | L4-L4 | 32–33 | 2 | average | 1.38 |
uEPSP amplitude in mV for excitatory connections between identified cell-types and/or layers in neocortex.
Included studies predominantly quantified synaptic properties for a targeted connection. Extended connection matrices are available in Reyes and Sakmann (1999), Lefort et al. (2009), , and .
A recent study has shown that the total extracellular Ca2+ in human cerebral spinal fluid can be as low as 1.2 mM (∼1.0 mM free Ca2+ (). Since the Ca2+ concentration has been shown to affect neuronal excitability, presynaptic release probability and short-term synaptic plasticity (Molnar et al., 2016; ), it is crucial to incorporate this parameter into the comparison of synaptic strength across different studies. Recording temperature also affects synaptic release probability (hence: uEPSP amplitude), failure rate, reliability (), or synaptic plasticity (Klyachko and Stevens, 2006) and the overview thus provides both Ca2+ concentration and recording temperature at which the synaptic strength was quantified.
Perhaps the best-studied neuronal microcircuits are the primary somatosensory (S1) and primary visual (V1) cortices (Reyes and Sakmann, 1999; Lefort et al., 2009; ; ; Markram et al., 2015; Seeman et al., 2018; ). Depending on the specific connection between excitatory cell types within or across layers, the EPSP amplitude at the soma can vary considerably (Figure 1 and Table 2). For example, the EPSP amplitude for the unitary connection between presynaptic L6A cortico-thalamic pyramidal neurons and a L6A excitatory cell type as postsynaptic target (in S1) is 0.09 mV (Yang et al., 2021b). A connection with a much larger mean unitary EPSP (uEPSP) amplitude is between L4 excitatory neurons (i.e., 1.38 mV) (Qi et al., 2017) and multiple EPSP amplitude values have been reported to fall within this range (Figure 1 and Tables 1, 2). The unitary synaptic connection between pyramidal neurons in cortical layers 2 and 3 has been characterized in several studies. They show substantial differences in the mean or median uEPSP amplitude for L2/3 pyramidal-to-pyramidal cell connections across different cortical regions (PFC, TeA, S1, V1, MTG) and species (mouse, rat, macaque, human; total range: 0.18–2.01 mV, Figure 1 and Table 1). Experimental or analytical conditions such as developmental stage (i.e., juvenile, adolescent, adult), external Ca2+ (1.3, 1.8, 2.0, 2.5 or 3.0 mM), temperature or reported mean/median could certainly influence the reported uEPSP amplitude, but it is also likely that the synaptic strength is dependent on the connection established between different L2/3 pyramidal cell types (; ; ; ). Pyramidal-to-interneuron or interneuron-to-pyramidal cell connections are typically stronger (Molnar et al., 2016; Wilbers et al., 2023), but here we focus on synaptic transmission between pairs of excitatory neurons. In this context, it is important to emphasize that amplitude distributions are typically skewed with the majority of connections showing small amplitudes and a long tail of stronger connections (; ; Song et al., 2005; ; Seeman et al., 2018; ). We would therefore argue that the median (and 1st-3rd interquartile ranges) should be consistently reported as it is more representative for the skewed population data. Ideally, these population statistics are also supplemented with the full range (min/max) of the population data as the extremes of the lognormal distribution may have biologically relevant functions (Szegedi et al., 2016, 2017). Synaptic connections with small mean uEPSP amplitudes may also fall below the detection power [Seeman et al., 2018; Supplementary Figure 14 in and Supplementary Figure 3 in Qi and Feldmeyer (2016)], especially when using a limited number of sweeps to probe for the presence of a connection. The combination of small amplitude connections and low detection power increases the false negative rate, underestimates the true connectivity, and may lead to an overestimation of mean EPSP amplitude of a given synaptic connection type. It is therefore perhaps not surprising that connections with a small uEPSP amplitude may be missed by electrophysiological recordings from the soma [but see Yang et al. (2021b)], but are reliably detected using EM techniques (Loomba et al., 2022). However, the use of EM techniques has also limitations when studying wiring diagrams because the axonal arbors occupy much larger volumes relative to the tissue blocks currently processed for EM examination (Oberlaender et al., 2011; Narayanan et al., 2015; Winnubst et al., 2019). Therefore, cross-scale techniques including correlated anatomical and physiological measurements are still urgently needed to generate a comprehensive, functional wiring diagram for microcircuits of interest.
For a given connection type, population distributions of uEPSP amplitude can thus show a pronounced skew with a subset of unitary connections being particularly strong and even sufficiently large to evoke AP firing (, ; ; Silver et al., 2003; Song et al., 2005; ; Lefort et al., 2009). These exceptionally strong excitatory connections are attractive to study because in vivo recordings from primary somatosensory and primary visual cortices have shown that a small subset of excitatory neurons show a particularly strong response to sensory stimulation, while the majority of neurons respond with only a subthreshold depolarization or not all, [e.g., (; ; Kerr et al., 2007; O’Connor et al., 2010; ; ; ; )]; these neurons can be referred to as ‘high responders’. A systematic analysis of the properties of these ‘high responder’ neurons and the impact of large uEPSPs is still lacking and as such a matter of debate. It would be interesting to determine whether particularly strong intracortical synapses go hand in hand with reliable sensory representation in vivo (Yassin et al., 2010).
For neurons with dendrites that are electrically relatively compact [e.g., rodent neurons, ()], detection power may not be a major issue as distal synapses can still have a profound impact on the somatic membrane potential. However, cortical neurons of human brain have much longer dendrites as well as increased branching (Mohan et al., 2015). The outcome of these extended morphologies is a huge capacitance load on electrical signals traveling from distal regions to the soma resulting in electrically isolated subcompartments (; ; ). Therefore, the risk of false negative connections increases substantially when probing human cortical circuits (Seeman et al., 2018). The increased path length from dendrite to soma and potentially increased dendritic attenuation opens the possibility of evolutionary adaptation of human neurons. For example, one neurophysiological property that may compensate for this, is active dendritic electrogenesis, which has been extensively documented for somatosensory L5 thick tufted neurons (Larkum et al., 1999, 2022) and to some extent in pyramidal cells in layer 6 and superficial cortical layers (Ledergerber and Larkum, 2010, 2012). Depending on the type of synaptic input, dendritic electrogenesis will initiate voltage-dependent Ca2+ spikes in the apical dendrites or NMDA spikes in the basal dendrites and the apical tuft dendrites; these serve to amplify synaptic signals and ensure proper propagation to the soma (Larkum et al., 2022). Alternatively, it was suggested that human L2/L3 neurons may have a lower membrane capacitance compared to rodents (human: 0.5 μF/cm2, rodent: 1.0 μF/cm2, [(), but see ]. This potential adaptation could be specific to L2/L3 neurons () and translates to enhanced synaptic charge-transfer from dendrites to soma and ultimately similar EPSP amplitudes across species (Figure 1 and Table 1). Given the extended morphologies and increased path length of human neurons, it is even more important to understand the active properties of human dendrites in order to understand the passive and active propagation of synaptic inputs and ultimately neuronal input/output transformations (; ; Kalmbach et al., 2021; Testa-Silva et al., 2022).
Synaptic connections (and thus uEPSP amplitudes) are also affected by neuromodulatory transmitters such as acetylcholine and monoamines, by neuropeptides, and by many hormones all of which act by activating or deactivating ionotropic ion channels and/or G protein-coupled receptors (GPCRs). The release of these neuromodulators is dependent on circadian rhythm, behavioral state and age. Examples of neuromodulator receptors that cause an increase or decrease in the synaptic release probability include muscarinic and nicotinic acetylcholine receptors, as well as several types of serotonin and adenosine receptors [for reviews see Puig and Gulledge (2011), Radnikow and Feldmeyer (2018), Yang et al. (2021a)]. In addition, the released neurotransmitter may diffuse out of the synaptic cleft (‘spill over’) and affect the synaptic release probability by acting on G protein-coupled receptors (such as metabotropic glutamate receptors or GABAB receptors) in the perisynaptic membrane of the same or neighbouring presynaptic terminals (Kullmann and Asztely, 1998; Uchida et al., 2012; Wild et al., 2015). These neuromodulators are present in the cerebrospinal fluid at low micromolar concentrations and therefore affect synaptic release even in the absence of pharmacological intervention. The discovery of divergent gene expression of a major neuromodulatory receptor system between human and mouse (i.e., serotonin, (), calls for a detailed characterization of the interplay between baseline synaptic transmission in humans and the impact of the major neuromodulator systems.
Synaptic connections in the human neocortex
To date, only a small number of studies exist that have examined synaptic transmission at autapses (Yin et al., 2018) or between pairs of excitatory neurons in human brain (Komlosi et al., 2012; Szegedi et al., 2016; Seeman et al., 2018; Peng et al., 2019; ; ). The availability of human brain tissue is typically a by-product of neurosurgical resection of epileptic foci or tumors. This provides a window of opportunity to study synaptic transmission and quantify how neurons with overall larger morphologies, extended dendrites and most likely many more synaptic inputs than rodents deal with synaptic inputs. With only a handful of studies available, it is too premature to generalize, but the emerging data show common and divergent properties of synaptic transmission across species.
Measured at the soma, uEPSP amplitude for pyramidal-to-pyramidal cell connections in layer 2/3 across species is remarkably consistent (median ALL 0.46 mV, mouse: 0.43 mV, rat: 0.57 mV, macaque: 0.45 mV, human: 0.48 mV, Figure 1 and Table 1). This suggests that obvious differences in the principles of brain organization or neuronal architecture do not affect the fundamental unit of synaptic information transfer. Examples of these differences in organizational principles across species include brain mass [mouse 0.417 g, human 1,508 g, (), the number of cortical neurons (mouse: 2 billion, human: 16 billion, (), estimated spine count on an individual L2/3 pyramidal neuron (mouse: 10,000, human: 30,000, () or total dendritic length (mouse: 5.3 mm, human: 14.5 mm, (Mohan et al., 2015)]. These are just a few example differences, but can easily be extended to dendritic path length, synapse density, and many more (; Yakoubi et al., 2019a,b; Loomba et al., 2022). This certainly does not mean that everything is equal. A consistent finding now reported across two independent sites is that excitatory transmission is stronger in L2/L3 pyramidal-to-pyramidal connections for human compared to L2/3 in mouse (; ), which could be (in part) explained by increased contribution of NMDA receptor activation during unitary synaptic transmission in humans but not mice. Alternatively, increased synaptic strength can be the outcome of a difference in presynaptic release probability (). A second consistent finding is that recovery from synaptic depression is faster in humans compared to mice (Testa-Silva et al., 2014; ; ). These differences have implications for the cellular information transfer, signal flow within neuronal microcircuits and thus ultimately cognition and mental ability ().
Conclusion and outlook
The synapse is the fundamental building block of neuronal microcircuits across species. The anatomical features (), functional properties (Seeman et al., 2018; ; ), and plasticity dynamics (Testa-Silva et al., 2014) differ when comparing pyramidal-to-pyramidal cell connections in cortical L2/3 in human and mouse. Comparable differences in anatomy (Yakoubi et al., 2019a,b) or physiology (Molnar et al., 2016) have also been described in deeper layers or pyramidal-to-interneuron connections, respectively, suggesting a spectrum of human-specific adaptations in synaptic transmission. As we are only beginning to see the tip of the iceberg and much remains unknown about synaptic transmission in human (and non-human primates), it will be critical to continue efforts to study synaptic transmission in the human brain between identified cell types. This will accelerate efforts to build realistic biophysical models of individual neurons (; ), microcircuit simulations (Markram et al., 2015; ) and ultimately facilitate a comprehensive understanding of human cognitive abilities in health and disease.
Statements
Author contributions
CK: Conceptualization, Funding acquisition, Writing—original draft, Writing—review and editing. DF: Conceptualization, Funding acquisition, Writing—original draft, Writing–review and editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Institute of Mental Health (BICAN) grant UM1MH130981-01 (CK) and by The Dutch Research Council (NWO) Open Competition (ENW-M2) grant nr OCENW.M20.285 (CK), the Helmholtz Society (DF) and European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Framework Partnership Agreement No. 650003 (HBP FPA) (DF).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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Summary
Keywords
excitatory neurotransmission, rodent, primate, human, synapse, EPSP, neocortex
Citation
de Kock CPJ and Feldmeyer D (2023) Shared and divergent principles of synaptic transmission between cortical excitatory neurons in rodent and human brain. Front. Synaptic Neurosci. 15:1274383. doi: 10.3389/fnsyn.2023.1274383
Received
08 August 2023
Accepted
21 August 2023
Published
05 September 2023
Volume
15 - 2023
Edited by
Karri P. Lamsa, University of Szeged, Hungary
Reviewed by
Viktor Szegedi, Hungarian Centre of Excellence for Molecular Medicine (HCEMM), Hungary; Eric Hanse, University of Gothenburg, Sweden
Updates
Copyright
© 2023 de Kock and Feldmeyer.
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*Correspondence: Christiaan P. J. de Kock, ckock@falw.vu.nlDirk Feldmeyer, d.feldmeyer@fz-juelich.de
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