Areti, A. | bioRxiv Science

bioRxiv2025

UNWANTED AXON GROWTH: PTEN AND THE SUPPRESSION OF AXON PLASTICITY IN ADULT NERVES

In adults, peripheral nerves comprise bundles of disseminated motor, sensory and autonomic axons that are considered stable neuroanatomical units. The only exceptions to this established wiring are very distal terminal branches in target organs, such as skin. Here we provide a remarkable deviation from this state of affairs in the peripheral nerves of mice with a conditional knockout of sensory neuron PTEN (phosphatase and tensin homolog deleted on chromosome ten). PTEN is normally expressed in adult sensory neurons, particularly small IB4 nonpeptidergic subtypes and its knockdown after injury or during experimental diabetes improves axon regrowth. We studied Advillin Cre;PTEN null mice lacking PTEN in their sensory neurons. As might be expected, their harvested and cultured DRG neurons displayed enhanced neurite outgrowth in vitro. In vivo, these mice were healthy and had a normal sensory behavioural phenotype. However, the nerves of mice lacking sensory neuron PTEN were highly abnormal, with augmented clusters of small myelinated and unmyelinated axons populating endoneurial fascicles of their peripheral nerve trunks. The axon clusters did not disrupt normal fascicular anatomy but invested the epidermis with greater axon numbers. Within endoneurial fascicles, supernumerary axons formed regenerative units and expressed ongoing growth markers, unlike normal adult axons. This was not accompanied by rises in dorsal root ganglia (DRG) neuron numbers, indicating enhanced distal sprouting from parent neurons. Additionally, sprouting axons were electrophysiologically intact, generating rises in the amplitudes of sensory nerve action potentials. Despite this extensive regenerative activity of intact nerves, regeneration indices after superimposed injury were only modestly enhanced or unchanged. This unusual behaviour of adult sensory axons lacking a single growth-suppressive molecule may identify insights into what molecular constraints the nervous system normally utilizes to suppress inappropriate plasticity.

neuroscience↗

bioRxiv2023

Individual-specific memory reinstatement patterns within human face-selective cortex

Humans have the remarkable ability to vividly retrieve sensory details of past events. According to the theory of sensory reinstatement, during remembering, brain regions involved in the sensory processing of prior events are reactivated to support this perception of the past. Recently, several studies have emphasized potential transformations in the spatial organization of reinstated activity patterns. In particular, studies of scene stimuli suggest a clear anterior shift in the location of retrieval activations compared with those during perception. However, it is not clear that such transformations occur universally, with evidence lacking for other important stimulus categories, particularly faces. Critical to addressing these questions, and to studies of reinstatement more broadly, is the growing importance of considering meaningful variations in the organization of sensory systems across individuals. Therefore, we conducted a multi-session neuroimaging study to first carefully map individual participants face-selective regions within ventral temporal cortex (VTC), followed by a second session to examine the correspondence of activity patterns during face memory encoding and retrieval. Our results showed distinct configurations of face-selective regions within the VTC across individuals. While a significant degree of overlap was observed between face perception and memory encoding, memory retrieval engagement exhibited a more selective and constricted reinstatement pattern within these regions. Importantly, these activity patterns were consistently tied to individual-specific neural substrates, but did not show any consistent direction of spatial transformation (e.g., anteriorization). To provide further insight to these findings, we also report on unique human intracranial recordings from VTC under the same experimental conditions. Our findings highlight the importance of considering individual variations in functional neuroanatomy in the context of assessing the nature of cortical reinstatement. Consideration of such factors will be important for establishing general principles shaping the neural transformations that occur from perception to memory.

neuroscience↗