The Beholder’s Share: Bridging art and neuroscience to study individual differences in subjective experience

Proceedings of the National Academy of Sciences · 2025-04-07 · 3 citations

Our experience of the world is inherently subjective, shaped by individual history, knowledge, and perspective. Art offers a framework within which this subjectivity is practiced and promoted, inviting viewers to engage in interpretation. According to art theory, different forms of art-ranging from the representational to the abstract-challenge these interpretive processes in different ways. Yet, much remains unknown about how art is subjectively interpreted. In this study, we sought to elucidate the neural and cognitive mechanisms that underlie the subjective interpretation of art. Using brain imaging and written descriptions, we quantified individual variability in responses to paintings by the same artists, contrasting figurative and abstract paintings. Our findings revealed that abstract art elicited greater interindividual variability in activity within higher-order, associative brain areas, particularly those comprising the default-mode network. By contrast, no such differences were found in early visual areas, suggesting that subjective variability arises from higher cognitive processes rather than differences in sensory processing. These findings provide insight into how the brain engages with and perceives different forms of art and imbues it with subjective interpretation.

CHAPTER 4 PORTRAITURE AND THE BEHOLDER’S SHARE

Columbia University Press eBooks · 2024-04-25

Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction

Molecular Psychiatry · 2024-11-23 · 5 citations

Abstract Fear extinction leads to a decrease of originally acquired fear responses after the threat is no longer present. Fear extinction is adaptive and critical for organism’s survival, but deficits in extinction may lead to exaggerated fear in animals or post-traumatic stress disorder (PTSD) in humans. Dopamine has recently emerged as essential for fear extinction and PTSD, however the neural circuits serving this dopamine function are only beginning to be investigated, and the dopamine intracellular signaling pathways are unknown. We generated gastrin-releasing peptide gene knockout ( Grp -/- ) mice and found that they exhibit enhanced fear memory in a stress-enhanced fear learning (SEFL) paradigm, which combines stress exposure and fear extinction, two features critical for developing PTSD. Using in vivo fiber photometry to record dopamine signals, we found that the susceptibility of Grp -/- mice to SEFL is paralleled by an increase in basolateral amygdala (BLA) dopaminergic binding during fear conditioning and early extinction. Combined optogenetics and ex vivo electrophysiology showed an increase in presynaptic ventral tegmental area (VTA)-BLA connectivity in Grp -/- mice, demonstrating a role of dysregulated input from the VTA on BLA function in the absence of the GRP. When examining gene transcription using RNA-seq and qPCR, we discovered concerted down-regulation in dopamine-related genes in the BLA of Grp -/- mice following long-term SEFL memory recall that was not observed in naïve conditions. These experiments demonstrate that the GRP regulates dopamine function in stress-enhanced fear processing and identify the Grp as the first gene known to regulate dopaminergic control of fear extinction.

The creative brain—an edited excerpt from ‘Essays on Art and Science’

The Transmitter · 2024-01-01

CHAPTER 3 COMPETING INFLUENCES THAT GAVE RISE TO THE MODERN REPRESENTATION OF WOMEN

Columbia University Press eBooks · 2024-04-25

CPEB3 low-complexity motif regulates local protein synthesis via protein–protein interactions in neuronal ribonucleoprotein granules

Proceedings of the National Academy of Sciences · 2023-01-30 · 16 citations

Biomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs) are a type of biomolecular condensate necessary for local protein synthesis and are involved in synaptic plasticity and long-term memory. Most of the proteins in RNPs possess low-complexity motifs (LCM), allowing for increased promiscuity of protein-protein interactions. Here, we describe the importance of protein-protein interactions mediated by the LCM of RNA-binding protein cytoplasmic polyadenylation element binding protein 3 (CPEB3). CPEB3 is necessary for long-term synaptic plasticity and memory persistence, but the mechanisms involved are still not completely elucidated. We now present key mechanisms involved in its regulation of synaptic plasticity. We find that CPEB3-LCM plays a role in appropriate local protein synthesis of messenger ribonucleic acid (mRNA) targets, through crucial protein-protein interactions that drive localization to neuronal Decapping protein 1 (DCP1)-bodies. Translation-promoting CPEB3 and translation-inhibiting CPEB1 are packaged into neuronal RNP granules immediately after chemical long-term potentiation is induced, but only translation-promoting CPEB3 is repackaged to these organelles at later time points. This localization to neuronal RNP granules is critical for functional influence on translation as well as overall local protein synthesis (measured as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) insertion into the membrane and localization to the synapse). We therefore conclude that protein-protein interaction between the LCM of CPEB3 plays a critical role in local protein synthesis by utilizing neuronal RNP granules.

Distribution, cellular localization, and colocalization of several peptide neurotransmitters in the central nervous system of<i>Aplysia</i>

Learning & Memory · 2023-05-01 · 1 citations

Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been hampered by the complexity of the nervous system. The marine mollusk Aplysia , with a simpler nervous system and many large, identified neurons, presents several advantages for addressing this question and has been used to examine the roles of tens of peptides in behavior. To screen for other peptides that might also play roles in behavior, we observed immunoreactivity in individual neurons in the central nervous system of adult Aplysia with antisera raised against the Aplysia peptide FMRFamide and two mammalian peptides that are also found in Aplysia , cholecystokinin (CCK) and neuropeptide Y (NPY), as well as serotonin (5HT). In addition, we observed staining of individual neurons with antisera raised against mammalian somatostatin (SOM) and peptide histidine isoleucine (PHI). However, genomic analysis has shown that these two peptides are not expressed in the Aplysia nervous system, and we have therefore labeled the unknown peptides stained by these two antibodies as X SOM and X PHI . There was an area at the anterior end of the cerebral ganglion that had staining by antisera raised against many different transmitters, suggesting that this may be a modulatory region of the nervous system. There was also staining for X SOM and, in some cases, FMRFamide in the bag cell cluster of the abdominal ganglion. In addition, these and other studies have revealed a fairly high degree of colocalization of different neuropeptides in individual neurons, suggesting that the peptides do not just act independently but can also interact in different combinations to produce complex functions. The simple nervous system of Aplysia is advantageous for further testing these ideas.

The Beholder’s Share: Cross-subject Variability in Responses to Abstract Art

Journal of Vision · 2023-08-01

Subjective experience of art emerges from an interaction between external input, which is shared across individuals, and internal associations, which vary across individuals and give art its personal meaning. In art theory, the Beholder’s Share refers to the contribution a viewer makes to the meaning of a painting by drawing on a set of unique prior experiences. A key tenet of the Beholder’s Share is that a viewer brings more personal meaning to abstract art than to representational art. Here, we interrogate this theory. We reason that more personal meaning brought to a painting should manifest in variability across subjects in neural responses to the same painting. To test this, we scanned participants with fMRI while they viewed abstract or representational paintings. To determine whether subjects respond more subjectively to abstract vs. representational paintings, we measured cross-subject variability in patterns of BOLD activity. We found that abstract paintings elicited more variable patterns of BOLD activity, specifically in regions of the Default Mode Network, but not in low-level visual regions. This pattern is consistent with the idea that abstract paintings evoke more subjective high-level responses despite common visual input. Next, we leveraged neural networks to model how differences in individuals' prior visual experiences could drive the variability in high-level responses to abstract art. We simulated individual differences in visual experience using instances of the same neural network (ResNet50) trained on different visual data sets and compared across-network variability in activations for abstract and representational paintings. We found that representations varied across networks more for abstract paintings than for representational paintings. Complementing the fMRI results, this pattern was found specifically in higher layers of the network. Overall, these studies provide insight into a possible neural instantiation of the Beholder’s Share and how it may emerge from individual differences in prior experience.

SUMO2 Protects Against Tau-induced Synaptic and Cognitive Dysfunction

bioRxiv (Cold Spring Harbor Laboratory) · 2022-11-13 · 5 citations

Summary Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer’s disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD), which can be caused by mutations of Tau. Mutated and pathological Tau can undergo a range of post-translational modifications (PTMs) that might trigger or modulate disease pathology. Recent studies indicate that modification of wild type Tau by S mall u biquitin-like m odifier SUMO isoform 1 (SUMO1) controls Tau hyperphosphorylation and aggregation, suggesting that SUMOylation acts as a central regulator of Tau’s biochemical properties. Besides SUMO1, Tau is modified by SUMO2/3, however the consequences of this modification have not been investigated. Here, using viral approaches on primary hippocampal neurons, transgenic mice expressing mutant Tau and SUMO2, and iPSC-derived neurons from FTD patients, we evaluated whether SUMO2/3 conjugation modifies the neurodegenerative disease pathology associated with the aggregation-prone mutant Tau P301L, P301S, and R406W variants. We found that mutant forms of Tau are targets of SUMO2/3, and SUMO2/3 conjugation is neuroprotective. Importantly, expression of mutant Tau is accompanied by a significant reduction of SUMO2/3 conjugation levels, and restoring levels of SUMO2 reduces mutant Tau aggregation and phosphorylation in all model systems Furthermore, overexpression of SUMO2 restores levels of pre- and post-synaptic markers, associated with a complete rescue of the LTP and memory deficits in transgenic mice expressing mutant Tau. These findings bring to light the potential therapeutic implication of manipulating SUMO conjugation to detoxify Tau through PTM-based approaches.

A missense mutation in <i>Kcnc3</i> causes hippocampal learning deficits in mice

Proceedings of the National Academy of Sciences · 2022-07-26 · 2 citations

Although a wide variety of genetic tools has been developed to study learning and memory, the molecular basis of memory encoding remains incompletely understood. Here, we undertook an unbiased approach to identify novel genes critical for memory encoding. From a large-scale, in vivo mutagenesis screen using contextual fear conditioning, we isolated in mice a mutant, named Clueless , with spatial learning deficits. A causative missense mutation (G434V) was found in the voltage-gated potassium channel, subfamily C member 3 ( Kcnc3) gene in a region that encodes a transmembrane voltage sensor. Generation of a Kcnc3 G434V CRISPR mutant mouse confirmed this mutation as the cause of the learning defects. While G434V had no effect on transcription, translation, or trafficking of the channel, electrophysiological analysis of the G434V mutant channel revealed a complete loss of voltage-gated conductance, a broadening of the action potential, and decreased neuronal firing. Together, our findings have revealed a role for Kcnc3 in learning and memory.