One exception was extensive connectivity between ExNs and A-delta-LTMR and C-LTMR modules revealing convergence between fast and slow conducting LTMR pathways. Radial cells were between first and second layers and had direct Sst+ C-HTMR/Heat input. Vertical cells were in the third network layer. /19
October 13, 2026 at 9:45 PM
One exception was extensive connectivity between ExNs and A-delta-LTMR and C-LTMR modules revealing convergence between fast and slow conducting LTMR pathways. Radial cells were between first and second layers and had direct Sst+ C-HTMR/Heat input. Vertical cells were in the third network layer. /19
Traversal was repeated 10000 times and defined each neuronal layer as the mean step at which it was traversed. ExNs in A-delta-HTMR, C-HTMR/Heat, C-LTMR and A-delta-LTMR modules were positioned in the second layer. These modules received little input from the other ExNs. /18
October 13, 2026 at 9:45 PM
Traversal was repeated 10000 times and defined each neuronal layer as the mean step at which it was traversed. ExNs in A-delta-HTMR, C-HTMR/Heat, C-LTMR and A-delta-LTMR modules were positioned in the second layer. These modules received little input from the other ExNs. /18
69+-18% from C-HTMR/Heat-module of the corresponding fiber(MrgprD+, MrgprB4+, MrgprA3+), 82+-10% in C-LTMR module and 77+-11 in A-delta-LTMR. All these modules had diverse morphologies but could be classified as central cells. Locations of these modules mirrored locations of their corresponding /9
October 13, 2026 at 9:45 PM
69+-18% from C-HTMR/Heat-module of the corresponding fiber(MrgprD+, MrgprB4+, MrgprA3+), 82+-10% in C-LTMR module and 77+-11 in A-delta-LTMR. All these modules had diverse morphologies but could be classified as central cells. Locations of these modules mirrored locations of their corresponding /9
their axodendritic and dendrodendritic synapses onto C-HTMR/Heat module ExNs. Similarly with the Islet-PSI-IhN Aδ-LTMR. However, Islet-PSI-IhN C-LTMR and PSI-IhNAδ-HTMRs targeted both their homotypic pathways and onto C-HTMR/Heat modules. Notably, PSI-IhNAδ-HTMRs also directly inhibited /24
October 13, 2026 at 9:45 PM
their axodendritic and dendrodendritic synapses onto C-HTMR/Heat module ExNs. Similarly with the Islet-PSI-IhN Aδ-LTMR. However, Islet-PSI-IhN C-LTMR and PSI-IhNAδ-HTMRs targeted both their homotypic pathways and onto C-HTMR/Heat modules. Notably, PSI-IhNAδ-HTMRs also directly inhibited /24
The first major pathway linked LTMR, C-HTMR/Heat and a little A-delta-HTMR to R1 PNs through a multilayered feedforward network. This pathway accounted for 64.4% of all synapses in the network. P2 pathway integrated C-Cold, peptidergic C-fiber and polysynaptic LTMR and C-HTMR/Heat neurons. /21
October 13, 2026 at 9:45 PM
The first major pathway linked LTMR, C-HTMR/Heat and a little A-delta-HTMR to R1 PNs through a multilayered feedforward network. This pathway accounted for 64.4% of all synapses in the network. P2 pathway integrated C-Cold, peptidergic C-fiber and polysynaptic LTMR and C-HTMR/Heat neurons. /21
Islet-PSI-IhNC-HTMR/Heat, Islet-PSI-IhNC-LTMR, Islet-PSI-IhNAδ-LTMR, and PSI-IhNAδ-HTMR inhibitory neurons. Most of these IhN populations targeted their homotypic ExN modules as well as FFI synapses. Islet-PSI-IhNC-HTMR/Heat received inputs only from C-HTMR/Heat neurons and formed majority of/23
October 13, 2026 at 9:45 PM
Islet-PSI-IhNC-HTMR/Heat, Islet-PSI-IhNC-LTMR, Islet-PSI-IhNAδ-LTMR, and PSI-IhNAδ-HTMR inhibitory neurons. Most of these IhN populations targeted their homotypic ExN modules as well as FFI synapses. Islet-PSI-IhNC-HTMR/Heat received inputs only from C-HTMR/Heat neurons and formed majority of/23
P2-Nociceptive PNs, consistent with a role in suppressing nociceptive output to the brain. After that authors built a firing rate model. C-cold neurons activated P2-Cold and P2-nociceptive PNs with weak responses in other subtypes. C-LTMR and A-delta LTMRs activated P1PNs more strongly /25
October 13, 2026 at 9:45 PM
P2-Nociceptive PNs, consistent with a role in suppressing nociceptive output to the brain. After that authors built a firing rate model. C-cold neurons activated P2-Cold and P2-nociceptive PNs with weak responses in other subtypes. C-LTMR and A-delta LTMRs activated P1PNs more strongly /25
were putatively identified as the projection neurons. These neurons also had more elaborate and 3x bigger dendritic arbors. 6 PNs exhibited Gpr83+ like morphology with a one or more ventrally directed dendrites extending into LTMR zone sometimes reaching lamina 5. Genetic testing/11
October 13, 2026 at 9:45 PM
were putatively identified as the projection neurons. These neurons also had more elaborate and 3x bigger dendritic arbors. 6 PNs exhibited Gpr83+ like morphology with a one or more ventrally directed dendrites extending into LTMR zone sometimes reaching lamina 5. Genetic testing/11
a combination of LTMR, C-HTMR/Heat, C and A-delta nociceptors as well as the C-Cold inputs. This study provided a synaptic explanation to PN types describing cooling-selective, nociceptive-selective, and wide-dynamic-range. The P2-cold probably corresponds to cooling selective stuff. /27
October 13, 2026 at 9:45 PM
a combination of LTMR, C-HTMR/Heat, C and A-delta nociceptors as well as the C-Cold inputs. This study provided a synaptic explanation to PN types describing cooling-selective, nociceptive-selective, and wide-dynamic-range. The P2-cold probably corresponds to cooling selective stuff. /27
Based on morphologies and selectivity 5 types of interneurons were defined: islet-PSI-IhNC-HTMR/Heat, Islet-PSI-IhNC-LTMR, Islet-PSI-IhNAδ-LTMR, PSI-IhNAδ-HTMR, and PSI-IhNAβ-LTMR. EM analysis remarkably showed that these interneurons mostly received innervation from the same fibers that they/32
October 12, 2026 at 7:00 PM
Based on morphologies and selectivity 5 types of interneurons were defined: islet-PSI-IhNC-HTMR/Heat, Islet-PSI-IhNC-LTMR, Islet-PSI-IhNAδ-LTMR, PSI-IhNAδ-HTMR, and PSI-IhNAβ-LTMR. EM analysis remarkably showed that these interneurons mostly received innervation from the same fibers that they/32
A-beta RA-LTMR glomeruli received a median of 4 axoaxonic synapses per glomerulus, A-delta-LTMR, C-LTMR, MrgprD+ C-HTMR/Heat and dorsal A-delta-HTMR glomeruli receive 1-2 synapses, C-cold, MrgprA3+ C-HTMR/Heat, Sstr2+ С-Heat and Sst+ C-HTMR/Heat glomeruli and ventral axonal branches of A-delta /24
October 12, 2026 at 7:00 PM
A-beta RA-LTMR glomeruli received a median of 4 axoaxonic synapses per glomerulus, A-delta-LTMR, C-LTMR, MrgprD+ C-HTMR/Heat and dorsal A-delta-HTMR glomeruli receive 1-2 synapses, C-cold, MrgprA3+ C-HTMR/Heat, Sstr2+ С-Heat and Sst+ C-HTMR/Heat glomeruli and ventral axonal branches of A-delta /24
dendrodendritic synapses which have similar targets and FFI motifs as their axodendritic counterparts. Islet-PSI-IhNC-LTMR 82% targets were C-LTMR module neurons and 17% to C-HTMR/Heat module neurons. Islet-PSI-IhNC- HTMR/Heat inhibited C-HTMR/Heat modules almost exclusively. /44
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dendrodendritic synapses which have similar targets and FFI motifs as their axodendritic counterparts. Islet-PSI-IhNC-LTMR 82% targets were C-LTMR module neurons and 17% to C-HTMR/Heat module neurons. Islet-PSI-IhNC- HTMR/Heat inhibited C-HTMR/Heat modules almost exclusively. /44
formed axoaxonic synapses upon. This is what is known by homotypic PSI. Though PSI-IhNAβ-LTMR neurons received more heterotypic input: 3 out of 7 of these neurons receiced mostly A-beta-LTMR input, 2 out of 7 mostly received C-LTMR input( 58.2% and 46.8%) and the other 2 received A-delta-HTMR. /33
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formed axoaxonic synapses upon. This is what is known by homotypic PSI. Though PSI-IhNAβ-LTMR neurons received more heterotypic input: 3 out of 7 of these neurons receiced mostly A-beta-LTMR input, 2 out of 7 mostly received C-LTMR input( 58.2% and 46.8%) and the other 2 received A-delta-HTMR. /33
modules. For 75% of heterotypic PSI-IhNs the most frequently targeted module in heterotypic innervation was C-HTMR/Heat module neurons. Another way to inhibit local sensory neurons were the dendrodendritic synapses. Islet-PSI-IhN-C-LTMR and Islet-PSI-IhN-C-LTMR/Heat neurons formed thousands of/43
October 12, 2026 at 7:00 PM
modules. For 75% of heterotypic PSI-IhNs the most frequently targeted module in heterotypic innervation was C-HTMR/Heat module neurons. Another way to inhibit local sensory neurons were the dendrodendritic synapses. Islet-PSI-IhN-C-LTMR and Islet-PSI-IhN-C-LTMR/Heat neurons formed thousands of/43
Synapses on 1,553 postsynaptic spinal cord neurons. Here the inputs were less homotypic, E.g. Islet-PSI-IhNC-LTMR that receive >90% C-LTMR input formed synapses on C-HTMR/Heat input neurons(33.9%). And the PSI-IhNAδ-HTMR neurons received more input from C-HTMR/Heat neurons than Aδ-HTMRs. /40
October 12, 2026 at 7:00 PM
Synapses on 1,553 postsynaptic spinal cord neurons. Here the inputs were less homotypic, E.g. Islet-PSI-IhNC-LTMR that receive >90% C-LTMR input formed synapses on C-HTMR/Heat input neurons(33.9%). And the PSI-IhNAδ-HTMR neurons received more input from C-HTMR/Heat neurons than Aδ-HTMRs. /40
These results indicate that most PV+ interneurons both receive input from and preferentially inhibit Aδ-LTMRs, suggesting their identity as Islet-PSI-IhNAδ-LTMR. Notably, both PV+ PSI-IhNs and Islet-PSI-IhNAδ-LTMR neurons have myelinated axons supporting the idea that these PV+ IhNs are /38
October 12, 2026 at 7:00 PM
These results indicate that most PV+ interneurons both receive input from and preferentially inhibit Aδ-LTMRs, suggesting their identity as Islet-PSI-IhNAδ-LTMR. Notably, both PV+ PSI-IhNs and Islet-PSI-IhNAδ-LTMR neurons have myelinated axons supporting the idea that these PV+ IhNs are /38
different laminae it penetrated. This organization suggests abundance of PSI on LTMRs vs absence of it on thermoreceptors(Trpm8+ C-cold and Sstr2+ C-heat) and on itch-associated C-LTMR/Heat populations(MrgprA3+ and Sst+)./28
October 12, 2026 at 7:00 PM
different laminae it penetrated. This organization suggests abundance of PSI on LTMRs vs absence of it on thermoreceptors(Trpm8+ C-cold and Sstr2+ C-heat) and on itch-associated C-LTMR/Heat populations(MrgprA3+ and Sst+)./28
MrgprA3⁺, MrgprD⁺, and MrgprB4⁺ C-HTMR/Heat afferents frequently formed perforated boutons that were deeply invaginated by pre- and postsynaptic partners. C-LTMRs and Aδ-LTMRs exhibited a characteristic "beads-on-a-string" morphology. Aβ RA-LTMR terminals were larger in diameter. /13
October 12, 2026 at 7:00 PM
MrgprA3⁺, MrgprD⁺, and MrgprB4⁺ C-HTMR/Heat afferents frequently formed perforated boutons that were deeply invaginated by pre- and postsynaptic partners. C-LTMRs and Aδ-LTMRs exhibited a characteristic "beads-on-a-string" morphology. Aβ RA-LTMR terminals were larger in diameter. /13
thermoreceptors and Sst+/MrgprA3+ C-HTMR/Heat receiving almost none. However synapses formed from these IhNs to other neurons are mostly heterotypic. So it looks like PSI stays in the sensory channel, but on the other hand there are also a lot dendrodendritic synapses within C-LTMR and /50
October 12, 2026 at 7:00 PM
thermoreceptors and Sst+/MrgprA3+ C-HTMR/Heat receiving almost none. However synapses formed from these IhNs to other neurons are mostly heterotypic. So it looks like PSI stays in the sensory channel, but on the other hand there are also a lot dendrodendritic synapses within C-LTMR and /50
(SPinal cord Integrated NEuron classifier) to identify neuronal types in DH based on their connectivity. LTMR mechanoreceptors seem to form way more synapses than any others and receive the most PSI. Also 5 types of inhibitory spinal neurons were identified (IhNs) each presynaptically inhibiting/2
October 12, 2026 at 7:00 PM
(SPinal cord Integrated NEuron classifier) to identify neuronal types in DH based on their connectivity. LTMR mechanoreceptors seem to form way more synapses than any others and receive the most PSI. Also 5 types of inhibitory spinal neurons were identified (IhNs) each presynaptically inhibiting/2
and formed fewer discrete boutons. The ground-truth dataset in dSC1 had 2057 neuron cutouts and had 8 classes(MrgprA3+, MrgrprD+ and MrgprB4+ in one class). A-beta LTMR subtypes also could not be reliably distinguished from one another (due to lack of genetic tools) /14
October 12, 2026 at 7:00 PM
and formed fewer discrete boutons. The ground-truth dataset in dSC1 had 2057 neuron cutouts and had 8 classes(MrgprA3+, MrgrprD+ and MrgprB4+ in one class). A-beta LTMR subtypes also could not be reliably distinguished from one another (due to lack of genetic tools) /14
E.g. A-beta LTMR forms 17000 synapses while HTMR can have only up to a 100 synapses. This suggests how different touch subcircuits are different comparing to other modalities. Strikingly for LTMRs their synapses are formed on the tips of axonal branches suggesting that each branch could be/48
October 12, 2026 at 7:00 PM
E.g. A-beta LTMR forms 17000 synapses while HTMR can have only up to a 100 synapses. This suggests how different touch subcircuits are different comparing to other modalities. Strikingly for LTMRs their synapses are formed on the tips of axonal branches suggesting that each branch could be/48
Also some of these synapses participated in triadic motifs involving a sensory afferent, and a FFInhibited spinal neuron. Apprx 15% of axodendritic synapses made C-LTMR and MrgprD+ C-HTMR/Heat afferents and 10% of those made by MrgprA3+ C-HTMR/Heat afferents were in these triads. /45
October 12, 2026 at 7:00 PM
Also some of these synapses participated in triadic motifs involving a sensory afferent, and a FFInhibited spinal neuron. Apprx 15% of axodendritic synapses made C-LTMR and MrgprD+ C-HTMR/Heat afferents and 10% of those made by MrgprA3+ C-HTMR/Heat afferents were in these triads. /45
postsynaptic sensory modules belonged to neurons within the C-HTMR/Heat modules, and 29% of Islet-PSI-IhNC-LTMR postsynaptic sensory modules also belonged to C-HTMR/Heat module neurons. The exception were Islet-PSI-C-HTMR/Heat neurons which formed synapses almost exclusively onto C-HTMR/Heat . /42
October 12, 2026 at 7:00 PM
postsynaptic sensory modules belonged to neurons within the C-HTMR/Heat modules, and 29% of Islet-PSI-IhNC-LTMR postsynaptic sensory modules also belonged to C-HTMR/Heat module neurons. The exception were Islet-PSI-C-HTMR/Heat neurons which formed synapses almost exclusively onto C-HTMR/Heat . /42
enter the spinal cord and extend along the rostral-caudal axis to form multiple axon collateral in the gray matter. All LTMRs formed more axodendritic synapses(2,662 ± 86 for Adelta and 2,532 ± 316 for C) than A-delta HTMRs, peptidergic and TRPM8s. A-beta-LTMR collateral formed 1,772 ± 360 ./21
October 12, 2026 at 7:00 PM
enter the spinal cord and extend along the rostral-caudal axis to form multiple axon collateral in the gray matter. All LTMRs formed more axodendritic synapses(2,662 ± 86 for Adelta and 2,532 ± 316 for C) than A-delta HTMRs, peptidergic and TRPM8s. A-beta-LTMR collateral formed 1,772 ± 360 ./21