Investigation of affective input during object encoding in the perirhinal cortex

Informazioni relative al progetto

EmotionObjectCoding

ID dell’accordo di sovvenzione: 101063718

DOI

10.3030/101063718

Progetto chiuso

Data della firma CE 22 Luglio 2022

Data di avvio 1 Maggio 2023

Data di completamento 30 Aprile 2025

Finanziato da

• Marie Skłodowska-Curie Actions (MSCA)

Costo totale

Nessun dato

Contributo UE

€ 226 751,04

Coordinato da

NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Norway

Periodic Reporting for period 1 - EmotionObjectCoding (Investigation of affective input during object encoding in the perirhinal cortex)

Periodo di rendicontazione: 2023-05-01 al 2025-04-30

Sintesi del contesto e degli obiettivi generali del progetto

EmotionObjectCoding was a project aimed to advance our understanding of how affective input modulates sensory information processing in the brain, initially focused on how the basolateral amygdala (BLA) influences sensory encoding via its interactions with the perirhinal cortex (PER).

Despite the challenges encountered, the project made significant progress in the characterization of object encoding in the PER, particularly in the context of emotionally neutral stimuli. Using in-vivo electrophysiology (Neuropixel 1.0 and later 2.0) behavioral paradigms based on whisker deflection, high-speed video recording, and locomotion sensors, we identified novel patterns of PER activity that vary with behavioral state (e.g. stillness vs. locomotion). These findings revealed that behavioral state is processed differently in primary sensory cortices (such as somatosensory and auditory cortices) compared to associative regions like the PER and temporal association area (TeA), which display distinct encoding strategies more reflective of internal state or higher-order processing.

Furthermore, the project corroborated long-standing in-vitro findings showing poor information transfer from the PER to the ERC—an observation we now validated in-vivo through recordings during sensory stimulation. These results suggest that emotional valence, rather than sensory features alone, may be a critical factor for facilitating neural communication between cortical association areas and downstream regions, such as the Entorhinal cortex (ERC). This is particularly important in the context of understanding the neural basis of memory formation and could inform future studies on neuropsychiatric conditions in which these processes are disrupted or are maladapted, such as in the case of PTSD.

The scale and impact of the project are evidenced by two upcoming manuscripts: one as first author and one as co-author. These publications are expected to advance research in the PER, providing a valuable information of sensory information processing on this region, and what features are encoded in the activity of individual neurons. Additionally, the project laid the groundwork for the integration of positive and negative valence in future experiments in the host laboratory, particularly in the context of operant conditioning paradigms. This will further refine our understanding of how emotional relevance gates information transfer in cortico-hippocampal circuits.

In summary, the project provides novel mechanistic insight into the contextual modulation of sensory information processing and opens new avenues for exploring the affective gating of memory formation.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

During the reporting period, significant technical and scientific progress was made in order to explore in-vivo neuronal activity in the PER during a whisker deflection task in head-fixed mice.

I designed, built and troubleshooted a novel dual-Neuropixel 1.0 recording setup, which enabled simultaneous recordings from the PER, BAR and other cortical and associative areas. This setup also incorporated behavioral tracking of running speed and whisking. To investigate sensory information processing under neutral valence conditions, I implemented a custom tactile stimulation protocol using piezo actuators to deliver whisker deflections. Although efforts were made to implement a reward-based (positive valence) protocol using liquid reward (i.e. chocolate milk), technical challenges such as electrical noise and issues in operant conditioning training prevented the achievement of all the objectives. I did develop a solution for these issues using infrared lick detection, but I was unable to implement it within the timeline of this project.

Despite these limitations, the experiments provided a dataset that enabled us to analyze how sensory stimuli are processed across cortical regions. Notably, primary sensory areas like BAR exhibited strong stimulus discrimination capabilities at the population level, while the PER showed reduced discriminability, highlighting its distinct role in sensory integration. Analysis of spiking activity also revealed functionally diverse unit types within the PER, suggesting specialized roles in processing tactile information. Furthermore, firing rate comparisons across locomotion and stillness showed significant modulation in primary cortices but stable activity in association areas such as PER and TeA.

Progress on mapping inputs from the basolateral amygdala (BLA) to the PER was more limited. Due to the demanding nature of the in-vivo experiments in work package 1, the initial tracing experiments were not extended; however, existing retrograde tracing data in the host lab were analyzed. Unexpectedly, the majority of labeled neurons were found in the lateral amygdala (LA) rather than the BLA, suggesting species-specific differences from canonical models based largely on studies in cats. Furthermore, our in-vivo recordings from the PER and ERC revealed poor information transfer between these two areas, possibly due to strong local inhibition within the PER.

In summary, while the implementation of reward-related paradigms was not completed, the project delivered important insights into how the PER and related cortical areas respond to neutral tactile stimuli. The results suggest a context-dependent gating mechanism for information flow within the medial temporal lobe and raise new questions regarding the role of amygdalar nuclei in modulating PER activity.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

With the implementation of the tools I have developed during this fellowship, I believe that further research and experiments using these conditions will provide us with a much more definitive answer in regards to how affective valence information affects sensory information transmission between PER and ERC and potentially other downstream areas.