Endopiriform Neurons Projecting to Ventral CA1 are Critical for Recognition Memory

Core Concepts

Endopiriform neurons projecting to ventral CA1 (ENvCA1-proj. neurons) form a recurrent circuit with the piriform cortex and provide feedforward inhibition to ventral CA1 pyramidal neurons, playing a critical role in recognition memory.

Abstract

The content describes the circuit organization and functional significance of endopiriform (EN) neurons that project to the ventral CA1 (vCA1) region of the hippocampus. Key findings include:

EN represents a major afferent input to vCA1, with the number of EN neurons projecting to vCA1 being significantly higher than other known vCA1 afferents like the septum and amygdala.

ENvCA1-proj. neurons form reciprocal connections with the piriform cortex and provide potent feedforward inhibition to vCA1 pyramidal neurons, particularly targeting the GABAergic neurons in the proximal layers of vCA1.

In vivo calcium imaging showed that the activity of ENvCA1-proj. neurons is correlated with the time mice spend exploring novel stimuli, whether social or non-social.

Chemogenetic inhibition of ENvCA1-proj. neurons selectively impaired the memory-guided discrimination of familiar vs. novel stimuli, without affecting innate exploratory behavior or other cognitive functions like fear memory.

These results suggest that the ENvCA1-proj. circuit plays a critical role in recognition memory by balancing the responses to familiarity and novelty in vCA1 through feedforward inhibition and recurrent excitation within the endopiriform nucleus.

Stats

"The number of presynaptic neurons in EN was ∼10 fold lower than entorhinal cortex."
"The normalized count of presynaptic neurons in EN was significantly greater than basolateral amygdala, lateral septum, and medial septum."
"Around 30% of vCA1-projecting neurons were found to be double-labelled when a cortical injection was made into the prefrontal cortex."
"Connection probability and strength were lowest in neurons in SLM compared to neurons in other layers."
"The strength of IPSCs overwhelmed the EPSCs in all cases, indicating EN axons disynaptically inhibit pyramidal neurons in vCA1."

Quotes

"We found the piriform cortex contained highest number of presynaptic neurons followed by EN."
"Disruption of EN vCA1-proj. activity only impaired memory-guided exploration of novel stimuli without affecting innate exploration induced by novelty."

Key Insights Distilled From

Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory

by Yamawaki,N.,... at www.biorxiv.org 03-17-2024

https://www.biorxiv.org/content/10.1101/2024.03.17.585387v2

Deeper Inquiries

How do the recurrent circuits within the endopiriform nucleus contribute to the sustained attention to novelty

The recurrent circuits within the endopiriform nucleus play a crucial role in sustaining attention to novelty by facilitating the detection and processing of novel stimuli. These circuits create a feedback loop that enhances the activity of endopiriform neurons in response to novel inputs, leading to increased attention and focus on the unfamiliar stimuli. This sustained attention to novelty is essential for the encoding and consolidation of new information into memory. The recurrent connections within the endopiriform nucleus help maintain the heightened responsiveness to novel stimuli, ensuring that they are prioritized and processed effectively in the brain.

What are the potential mechanisms by which the feedforward inhibition from endopiriform to ventral CA1 modulates the responses to familiar vs. novel stimuli

The feedforward inhibition from the endopiriform nucleus to ventral CA1 modulates the responses to familiar vs. novel stimuli by regulating the activity of pyramidal neurons in the ventral CA1 region. This inhibition mechanism serves to suppress the activity of vCA1 pyramidal neurons in response to familiar stimuli, while allowing for enhanced activation in the presence of novel stimuli. By exerting inhibitory control over vCA1 pyramidal neurons, the endopiriform neurons shift the balance of neural activity towards novelty, promoting the detection and processing of new information. This modulation helps differentiate between familiar and novel stimuli, guiding memory-guided behavior towards exploring and responding to unfamiliar inputs.

What are the broader implications of the endopiriform-ventral CA1 circuit dysfunction in neuropsychiatric disorders characterized by recognition memory deficits

The dysfunction of the endopiriform-ventral CA1 circuit in neuropsychiatric disorders characterized by recognition memory deficits can have significant implications for cognitive function and behavior. Recognition memory is essential for various cognitive processes, including learning, decision-making, and social interactions. Disruptions in this circuit can lead to difficulties in distinguishing between familiar and novel stimuli, impairing the ability to form new memories and make informed decisions based on past experiences. In conditions such as Alzheimer's disease, schizophrenia, and attention-deficit/hyperactivity disorders, where recognition memory deficits are common, dysfunction in the endopiriform-ventral CA1 circuit may contribute to the cognitive symptoms observed in these disorders. Understanding and addressing these circuit dysfunctions could offer new insights into the underlying mechanisms of cognitive impairments and potential therapeutic targets for improving recognition memory in neuropsychiatric conditions.