Distinct neuronal populations contribute to trace conditioning and extinction learning in the hippocampal CA1.

Sudiksha Sridhar,Ali I Mohammed,Howard J Gritton,Xue Han,Moona Abdulkerim,Kyle R Hansen,Robb Kessel,Bobak Nazer,Rebecca A Mount

doi:10.7554/elife.56491

Abstract

Trace conditioning and extinction learning depend on the hippocampus, but it remains unclear how neural activity in the hippocampus is modulated during these two different behavioral processes. To explore this question, we performed calcium imaging from a large number of individual CA1 neurons during both trace eye-blink conditioning and subsequent extinction learning in mice. Our findings reveal that distinct populations of CA1 cells contribute to trace conditioned learning versus extinction learning, as learning emerges. Furthermore, we examined network connectivity by calculating co-activity between CA1 neuron pairs and found that CA1 network connectivity patterns also differ between conditioning and extinction, even though the overall connectivity density remains constant. Together, our results demonstrate that distinct populations of hippocampal CA1 neurons, forming different sub-networks with unique connectivity patterns, encode different aspects of learning.

Highlights

The hippocampus is critical for learning and memory in animals and humans
Calcium activity in CA1 neurons was monitored via GCaMP6f fluorescence, which allows recording from hundreds of neurons simultaneously (Mohammed et al, 2016; Chen et al, 2013; Gritton et al, 2019)
We provide the first detailed, real-time evidence that largely distinct populations of neurons within the hippocampal CA1 region respond to a trace conditioned stimulus during either conditioned learning or extinction learning

Summary

Introduction

The hippocampus is critical for learning and memory in animals and humans. Early surgical lesions of the hippocampus in human patients, designed to alleviate intractable epilepsy, resulted in severe memory loss and an inability to form new declarative or episodic memories (Scoville and Milner, 1957; Scoville, 1954). Various experimental paradigms have been devised to probe hippocampal-dependent forms of learning and memory. One such well-established paradigm is trace eye-blink conditioning, which requires an intact hippocampus (McEchron et al, 1998; Moyer et al, 2015; Tseng et al, 2004). In this experimental design, subjects are presented with a conditioned stimulus (CS), such as a tone or light, which reliably predicts an unconditioned stimulus (US), such as a puff of air or electrical shock delivered to the subject’s eyelid. Trace conditioning acquisition is thought to depend on signaling at both nicotinic and muscarinic acetylcholine receptors

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