The anterior cingulate cortex (ACC)—a component of both the limbic system and the frontal-executive network—is composed of three anatomically distinct subregions with diverse roles in processing cognitive and emotional information: rostral area 32 (A32), dorsal area 24 (A24), and ventral area 25 (A25). Pyramidal neurons (PYRs) as the neural substrates of cortical communication govern signal processing and integration differently across brain regions, layers, and pathways. Their properties and diversity across the heterogeneous ACC subregions have yet to be comprehensively characterized in primates. Here, we compared the biophysical and morphological properties of PYRs in layers 2-3 (L2-3) and 5-6 (L5-6) across ACC subregions of young adult rhesus monkeys (8 females, 11 males) using in vitro whole-cell patch-clamp recording with intracellular filling. Results showed the more pronounced laminar differences in biophysical properties of PYRs in A24 and A32 than in A25, with L2-3 PYRs exhibiting lower excitability than L5-6 PYRs. Further, A32 contained a higher proportion of PYRs receiving high-frequency-sEPSC and an enrichment of mushroom spines in L2-3 compared with L5-6. This heterogeneity in laminar differentiation aligns with cytoarchitectural differences across ACC subregions and suggests layer-specific signaling and excitatory drive in A24 and A32. In contrast, A25 showed cellular heterogeneity in firing patterns as well as different inhibitory signaling dynamics from other ACC subregions. Together, these results highlight the heterogeneity in laminar differentiation of PYR properties across ACC subregions, contributing to their diverse circuits and roles in cognitive-emotional integration and disruption in disease.
Yuxin Zhou, Maxine Hsiung, Angela L. Capriglione et al.· Journal of Neuroscience· 0 citations
Impaired activation of cortical circuits might contribute to working memory deficits in schizophrenia. In this disorder, layer 3 pyramidal neurons (L3PNs) of the prefrontal (PFC), primary visual (V1) and posterior parietal (PPC) cortices, three cortical areas essential for working memory, display alterations that may impair network activity. We review evidence suggesting that L3PN morphology and physiology differ significantly across PFC, PPC and V1 in primates. These differences are much less pronounced in rodents, suggesting a primate-enhanced regional variability that may be the substrate for area-specific L3PN vulnerability in schizophrenia. PFC L3PNs exhibit larger dendrites with higher spine density, thus substantially more excitatory synapses than V1 or PPC L3PNs. Furthermore, the PFC contains a unique stripe-like connectivity system mediated by the horizontal axon collaterals of L3PNs that might support robust recurrent excitation, and thus the mnemonic persistent activity thought to contribute to working memory storage. Physiologically, PFC L3PNs display higher spontaneous excitatory post-synaptic current (sEPSC) frequency and amplitude, indicating functionally more potent individual synapses in PFC than in V1 L3PNs. Although sEPSC differences are less pronounced between PPC and PFC L3PNs, the greater spine density in PFC suggests stronger excitatory drive in PFC L3PNs. We conclude by identifying open questions that are relevant for understanding schizophrenia pathophysiology: i) What are the sources of synaptic input on L3PNs in each area?, ii) What is the significance of dendritic spine density differences across areas?, and iii) Do NMDAR-mediated synaptic currents differ in strength between L3PNs in PFC, PPC, and V1?
G. González-Burgos, Ruth Benavides-Piccione, A. Neef et al.· Biological Psychiatry· 0 citations
