Mirror trends of plasticity and stability indicators in primate prefrontal cortex

Abstract

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases.

Microstructural and Functional Gradients are Increasingly Dissociated in Transmodal Cortices

“…The size, density and position of pyramidial neurons determine the total intracortical myelin content, as well as myelin banding. Histological studies have shown how this micro-scale correspondence confer similar macro-scale topographies, whereby laminar differentiation and mean intracortical myelin gradually change along the sensory-fugal gradient [54, [67][68][69]. Our findings extend upon this work by showing the global topography of myeloarchitectural similarity, which involves both mean myelin and myelin banding [66], is strongly related to macro-scale cytoarchitectural differentiation.…”

“…Importantly, the in vivo approach can serve as a lower resolution, yet biologically meaningful extension of the histological work. In fact, myelin-based gradients exhibited a comparable association with laminar differentiation and cytoarchitectural complexity as the histology-based gradient, as shown to be the case by earlier post mortem work [66][67][68][69]. Albeit replication of our findings at a vertex-wise level, the millimetre resolution of in vivo imaging may not always capture detailed spatial features visible on histology.…”

“…For example, prefrontal and parietal association regions bilaterally project feedforward and feedback connections [80], which can be densely interdigitated [81]. The diverse connectivity profiles in transmodal cortices are likely related to heightened synaptic plasticity [69] that enables more flexible reconfigurations of functional relationships. In contrast, synaptic plasticity is lower in sensory cortices where quick, accurate response to external stimuli necessitate a constrained hierarchical organisation [3].…”

A moment of change: shifts in myeloarchitecture characterise adolescent development of cortical gradients

“…Drifts in association cortex towards either sensory-like or paralimbic-like architecture represents, thus, an expansion of the sensory-fugal gradient of microstructural differentiation 18 . Such a sensory-fugal gradient was previously described by Mesulam 15 based on nonhuman primate research to encapsulate cortex-wide variations in architecture and connectivity, and has since been suggested to reflect increasing synaptic plasticity towards transmodal regions 52 . Systematic variations in the degree of experience-dependent plasticity may explain why myelin-derived markers develop differently along the sensory-fugal gradient 24 , in contrast to other known developmental gradients such as the rostro-caudal timing of terminal neurogenesis 53 .…”

Timescales of spontaneous fMRI fluctuations relate to structural connectivity in the brain

“…The spatial variation of intrinsic timescales has been measured using ECOG [21], MEG [25,26], TMS-EEG [27], and fMRI [24,[28][29][30][31][32][33], and may a function variation in temporal receptive windows: timescales over which new information can be actively integrated with recently received information [20,33,34]. Spatial variation in intrinsic activity fluctuations may form a key basis for the brain's functional hierarchical organization, shaped by structural variation in the brain's microcircuitry [35][36][37]. This organization is thought to be important for behavior and cognition [20,[38][39][40], and its disruption has clinical implications: e.g., differences in intrinsic timescales are associated with symptom severity in autism [33].…”