Multiple context discrimination in adult rats: sex variability and dynamics of time-dependent generalization of an aversive memory Fernanda Nogueira Lotz, Kétlyn Talise Knak Guerra, Ana Paula Crestani, Jorge Alberto Quillfeldt Learning and Memory, 2025 Memory generalization involves the transfer of conditioned fear responses to novel contexts, a phenomenon observed in systems consolidation, whereby a time-dependent reduction in discrimination precision occurs due to the reorganization of brain regions supporting memory retrieval. To understand the fine temporal structure of this process across sexes, young adult female and male rats were trained in contextual fear conditioning and tested in the same or one of three distinct novel contexts at 2, 28, or 45 days post-training. Neutral contexts were designed to allow graded levels of fear expression relative to the training context, and sex differences were evident at the recent memory test. This pattern, however, disappeared over time due to partial generalization, with fear converging into similar, higher values, grouped into two levels for both sexes. In all experiments, females were better discriminators and displayed lower fear responses than males, apparently prioritizing different sensory modalities, with multivariate analysis suggesting that chamber size was salient for females and floor texture for males. This study is the first to compare fear responses between adult female and male rats across multiple neutral contexts and time points revealing several dimorphic findings.
Human cortical amygdala dendrites and spines morphology under open-source three-dimensional reconstruction procedures Kétlyn T. Knak Guerra, Josué Renner, Carlos E. Vásquez, Alberto A. Rasia‐Filho Journal of Comparative Neurology, 2023 Visualizing nerve cells has been fundamental for the systematic description of brain structure and function in humans and other species. Different approaches aimed to unravel the morphological features of neuron types and diversity. The inherent complexity of the human nervous tissue and the need for proper histological processing have made studying human dendrites and spines challenging in postmortem samples. In this study, we used Golgi data and open‐source software for 3D image reconstruction of human neurons from the cortical amygdaloid nucleus to show different dendrites and pleomorphic spines at different angles. Procedures required minimal equipment and generated high‐quality images for differently shaped cells. We used the “single‐section” Golgi method adapted for the human brain to engender 3D reconstructed images of the neuronal cell body and the dendritic ramification by adopting a neuronal tracing procedure. In addition, we elaborated 3D reconstructions to visualize heterogeneous dendritic spines using a supervised machine learning‐based algorithm for image segmentation. These tools provided an additional upgrade and enhanced visual display of information related to the spatial orientation of dendritic branches and for dendritic spines of varied sizes and shapes in these human subcortical neurons. This same approach can be adapted for other techniques, areas of the central or peripheral nervous system, and comparative analysis between species.
The Subcortical-Allocortical- Neocortical continuum for the Emergence and Morphological Heterogeneity of Pyramidal Neurons in the Human Brain Alberto A. Rasia-Filho, Kétlyn T. Knak Guerra, Carlos Escobar Vásquez, Aline Dall’Oglio, Roman Reberger, et al. Frontiers in Synaptic Neuroscience, 2021 Human cortical and subcortical areas integrate emotion, memory, and cognition when interpreting various environmental stimuli for the elaboration of complex, evolved social behaviors. Pyramidal neurons occur in developed phylogenetic areas advancing along with the allocortex to represent 70–85% of the neocortical gray matter. Here, we illustrate and discuss morphological features of heterogeneous spiny pyramidal neurons emerging from specific amygdaloid nuclei, in CA3 and CA1 hippocampal regions, and in neocortical layers II/III and V of the anterolateral temporal lobe in humans. Three-dimensional images of Golgi-impregnated neurons were obtained using an algorithm for the visualization of the cell body, dendritic length, branching pattern, and pleomorphic dendritic spines, which are specialized plastic postsynaptic units for most excitatory inputs. We demonstrate the emergence and development of human pyramidal neurons in the cortical and basomedial (but not the medial, MeA) nuclei of the amygdala with cells showing a triangular cell body shape, basal branched dendrites, and a short apical shaft with proximal ramifications as “pyramidal-like” neurons. Basomedial neurons also have a long and distally ramified apical dendrite not oriented to the pial surface. These neurons are at the beginning of the allocortex and the limbic lobe. “Pyramidal-like” to “classic” pyramidal neurons with laminar organization advance from the CA3 to the CA1 hippocampal regions. These cells have basal and apical dendrites with specific receptive synaptic domains and several spines. Neocortical pyramidal neurons in layers II/III and V display heterogeneous dendritic branching patterns adapted to the space available and the afferent inputs of each brain area. Dendritic spines vary in their distribution, density, shapes, and sizes (classified as stubby/wide, thin, mushroom-like, ramified, transitional forms, “atypical” or complex forms, such as thorny excrescences in the MeA and CA3 hippocampal region). Spines were found isolated or intermingled, with evident particularities (e.g., an extraordinary density in long, deep CA1 pyramidal neurons), and some showing a spinule. We describe spiny pyramidal neurons considerably improving the connectional and processing complexity of the brain circuits. On the other hand, these cells have some vulnerabilities, as found in neurodegenerative Alzheimer’s disease and in temporal lobe epilepsy.
