Neurobiology of Memory

• Lecture about the neurobiology of memory
• Provides insight into the anatomy of the medial temporal lobe, its role in long-term memory, and the cellular basis of long-term memory.

Memory Processes

• Encoding is the process of transforming sensory data into a mental representation.
• Storage involves keeping encoded information in memory.
• Retrieval refers to pulling out or using information stored in memory.
• Source: Sternberg and Sternberg (2012)

Case Study: Henry Gustav Molaison (1926-2008)

• Underwent surgical removal of a large portion of the medial temporal lobes, including the hippocampus, as a treatment for intractable epilepsy.
• Developed anterograde amnesia, which impaired his ability to form new explicit memories.

Types of Memory

• Long-term memory
• Working memory

Neuroanatomy Terms

• Cortex: Latin for "shell"
• Lateral: side, from Latin "lateralis" (towards the side)
• Medial: towards the center, from Latin "medius" (middle)
• Gyrus: ridge, from Latin "gyrus" (circle)
• Sulcus: groove, from Latin "furrow"

Medial Temporal Lobe

• Plays a significant role in long-term memory
• The parahippocampal gyrus includes the perirhinal ("around "nose") and entorhinal ("inner" "nose") cortex.
• The hippocampus gets its name from the Greek words "hippos" (horse) and "kampos" (sea monster), resembling a sea horse.
• Receives input from the entorhinal cortex, and sends information through the entorhinal cortex and the fornix (Latin for "arch").

Neurological Evidence for Medial Temporal Lobe Role in Long-Term Memory

• Alzheimer’s disease is characterized by plaques and tangles in the medial temporal lobe.
• Atrophy of the medial temporal lobe is closely related to episodic memory deficits in Alzheimer's.
• Meta-analysis of 14 fMRI studies show healthy older adults exhibit increased neural response in the right hippocampus during episodic memory tasks, compared to Alzheimer's patients
• Terry et al., 2015, Journal of Neuroimaging

Animal Studies on Medial Temporal Lobe

• The delayed nonmatch-to-sample task is used to assess memory in primates (Mishkin, 1978).
• Primates are shown an object and, after a delay, must select a new object from the original and a new object.
• Primates with medial temporal lesions perform poorly on this task.
• The Morris water maze assesses spatial navigation learning in rats.
• Rats learn to locate a platform using visual cues, reducing the time to reach it over time.
• Rats with hippocampal lesions swim randomly.

Human fMRI Studies on Medial Temporal Lobe

• Subsequent-memory paradigm studies memory encoding in the hippocampus.
• fMRI scans the brains of Volunteers, who view the words of animate or inanimate objects either in red (animate) or green (size), for judgments based on color.
• Following the encoding phase, memory is tested with a mix of old and new items.

Subsequent-Memory Paradigm (Ranganath et al., 2004)

• Participants judge word size (green) or animacy (red) based on word color.
• The words are presented again later, mixed with new words, for confidence judgments.
• Examines neural response during encoding of correctly recollected items.
• Correctly recalled words are associated with increased neural response in the hippocampus and parahippocampal cortex.

Temporal Lobes and Memory Processes

• Aggleton and Brown (1999) propose that encoding processes for familiarity and recollection depend on different parts of the medial temporal lobes.
• Ranganath (2004) showed that higher perirhinal cortex activity correlates with increased recognition confidence (familiarity).
• Suggests the hippocampus is for recognition based on recollection, and the perirhinal cortex is for familiarity-based recognition.
• Montaldi et al., 2006 found this to be true for retrieval as well

Hippocampal Outflow

• Wheeler et al., 2000 observed neural activity during viewing (pictures, sounds) and recall.
• States that information from the hippocampus flows back to cortical sensory regions during recall.
• The reactivation of original cortical areas provided the encoding input to the hippocampus.

Frontal Cortex Role in Encoding and Retrieval

• The frontal cortex contributes to encoding and retrieval.
• Cabeza and colleagues theorize encoding involves the left frontal cortex, and retrieval involves the right frontal cortex.
• Kelley and colleagues theorize the left frontal cortex is involved in encoding/retrieval of linguistic data, and the right frontal cortex is involved in encoding/retrieval.

Memory Consolidation

• Process that stabilizes a memory over time after its initial acquisition.
• Rapid consolidation reliant on the hippocampus
• Slow permanent consolidation process
• Electroconvulsive therapy and head injury can cause retrograde amnesia.
• Items learned recently are most affected by ECT and head injuries providing evidence rapid consolidation.

Hippocampal Vulnerability

• Dannlowski et al. (2012) found childhood maltreatment is associated with reduced hippocampal volume (n = 145).
• The hippocampus is highly susceptible to stress and has a high expression of glucocorticoid receptors.

Cellular Basis of Memory

• Donald Hebb (1949) suggested learning has a biological basis - "cells that fire together wire together.”
• Santiago Ramon y Cajal (1894) proposed memory is stored through new connections between neurons.

Hebb's Law and Long-Term Potentiation

• Hebb’s law (1949):
• If a synapse is active when a postsynaptic neuron is active, the synapse will be strengthened.
• This is Hebbian learning.
• Also phrased as "cells that fire together wire together”.
• Bliss and Lømo (1973) found stimulation of axons in the rabbit hippocampus increased the magnitude of action potentials in downstream neurons.
• This is long-term potentiation (LTP).

Synaptic Mechanisms: Long-Term Potentiation

• Bliss and Lømo stimulated axons in the performant pathways.
• Resulted in a several-hour increase in exitatory postsynaptic potentials (EPSPs) in the granule cells of dentate gyrus.
• Source: Gazzaniga et al., 2014

Molecular Mechanisms of Long-Term Potentiation (LTP)

• NMDA (N-methyl-D-aspartate) receptors are normally blocked by magnesium.
• The receptors are opened once glutamate binds to the receptor and when the membrane is de-polarised
• Opening allows calcium ions to enter the cell.
• Calcium acts as an intracellular messenger, changing enzyme activities to influence synaptic strength.

Summary: Neurobiology of Long-Term Memory

• The medial temporal lobes' hippocampus and parahippocampal gyrus are important.
• Cellular mechanisms include long-term potentiation, "cells that fire together wire together," and NMDA receptors.