67: Prefrontal Cortex, Hippocampus, and the Biology of Explicit Memory Storage

Introduction

• Working Memory Depends on Persistent Neural Activity in the Prefrontal Cortex

  • Intrinsic Membrane Properties Can Generate Persistent Activity

  • Network Connections Can Sustain Activity

  • Working Memory Depends on the Modulatory Transmitter Dopamine

• Explicit Memory in Mammals Involves Different Forms of Long-Term Potentiation in the Hippocampus

  • Long-Term Potentiation in the Mossy Fiber Pathway Is Nonassociative

  • Long-Term Potentiation in the Schaffer Collateral Pathway Is Associative

  • Long-Term Potentiation in the Schaffer Collateral Pathway Follows Hebbian Learning Rules

  • Long-Term Potentiation Has Early and Late Phases

• Spatial Memory Depends on Long-Term Potentiation in the Hippocampus

• A Spatial Map of the External World Is Formed in the Hippocampus

• Different Subregions of the Hippocampus Are Required for Pattern Separation and for Pattern Completion

• Memory Also Depends on Long-Term Depression of Synaptic Transmission

• Epigenetic Changes in Chromatin Structure Are Important for Long-Term Synaptic Plasticity and Learning and Memory

• Are There Molecular Building Blocks for Learning?

• An Overall View

Explicit memory—the conscious recall of information about people, places, and objects—is what people commonly think of as memory. Sometimes called declarative memory, it binds our mental life together by allowing us to recall at will what we ate for breakfast, where we ate it, and with whom. It allows us to join what we did today with what we did yesterday or the week or month before that.

The two structures in the mammalian brain that are critical for encoding and storing explicit memories are the prefrontal cortex and the hippocampus. The prefrontal cortex mediates working memory (see Chapter 65). Information stored in working memory can be actively maintained for very short periods and then rapidly forgotten, such as a telephone number that is remembered only until it is dialed, or it can be stored elsewhere in the brain as long-term memory. The hippocampus stores declarative information in a more stable form for periods ranging from days to weeks to years, up to a lifetime. The ultimate storage site for all declarative memories is thought to be in the cerebral cortex. In this chapter we focus on the cellular and molecular mechanisms underlying working memory and long-term storage of explicit memories.

Working Memory Depends on Persistent Neural Activity in the Prefrontal Cortex

In vivo electrophysiological recordings from neurons in the prefrontal cortex of nonhuman primates have provided insights into the neural basis of working memory. Neuronal activity is measured while the animal is engaged in a delayed match-to-sample working memory task. In such tasks the animal is initially shown an image (the sample) and must retain the image in working memory for seconds to minutes after the initial image is extinguished (the delay period). The monkeys are then shown a test image and must press a lever to indicate whether the test image matches the sample image.

Neurons in the prefrontal cortex fire persistently during the delay period, presumably contributing to the ...