Neurobiology of Memory

• This lecture discusses the neurobiology of memory, focusing on the medial temporal lobe and cellular mechanisms of long-term memory.

Memory Processes

• Encoding transforms sensory data into mental representations.
• Storage keeps encoded information in memory.
• Retrieval pulls out or uses stored information.
• Source: Sternberg and Sternberg (2012)

Henry Gustav Molaison (1926 – 2008)

• Molaison underwent surgical removal of medial temporal lobes, including the hippocampus, as a treatment for intractable epilepsy.
• He later suffered anterograde amnesia and could not commit new events to his explicit memory.

Types of Memory

• Long-term memory is discussed.
• Working memory is covered.

Neuroanatomy Terms

• Cortex refers to the "shell" in Latin.
• Lateral means side, from the Latin word "lateralis."
• Medial means "towards the center," from the Latin word "medius."
• Gyrus is a ridge, derived from the Latin word "gyrus."
• Sulcus is a groove from the Latin word for "furrow".

Medial Temporal Lobe

• Plays a role in long-term memory
• The parahippocampal gyrus includes the perirhinal ("around nose") and entorhinal ("inner nose") cortex.

Hippocampus

• The word hippocampus comes from the Greek words "hippos" (horse) and "kampos" (sea monster), thus meaning sea horse.
• Receives input from the entorhinal cortex.
• Sends output via the entorhinal cortex and the fornix (Latin for "arch").

Evidence of Medial Temporal Lobe's Role in Long-Term Memory (Neurology)

• Alzheimer's disease causes plaques and tangles in the medial temporal lobe.
• Alzheimer's disease causes medial temporal lobe atrophy, related to deficits in episodic memory.
• Healthy older adults show increased neural response in the right hippocampus in episodic memory tasks, versus Alzheimer's patients. Research by Terry et al. from 2015 utilized fMRI for this research.

Role of Medial Temporal Lobe in Long-Term Memory (Animal Studies)

• A delayed nonmatch-to-sample task is used in primate research (Mishkin, 1978).
• Primates are shown an object and, after a delay, must select a new object when presented with the original and the new item.
• Primates with medial temporal lesions perform poorly on this delayed nonmatch-to-sample task.
• The Morris water maze (Morris, 1981) measures spatial navigation learning in rats.
• Over time, rats learn to reach a platform more quickly via visual cues.
• Rats with hippocampal lesions swim randomly in the maze.

Role of Medial Temporal Lobe in Long-Term Memory (Human fMRI)

• The subsequent-memory paradigm studies memory encoding in the hippocampus.
• Participants judge animate/inanimate items based on presented words in red (animate) or green (size).
• fMRI scans are performed while volunteers view words and make decisions (encoding phase).
• Memory is tested by presenting old items mixed with new items.
• Ranganath et al. (2004) used this subsequent-memory paradigm.
• Judgements about size (green) or animacy (red) are made based on word color.
• Participants rate confidence in recognizing previously seen words and identify the color they were presented in.
• Neural responses during encoding are examined for correctly recollected items.
• Correctly recollected words are linked to increased neural response in the hippocampus and parahippocampal cortex.

Recollection and Familiarity

• Aggleton and Brown (1999) suggest different parts of the medial temporal lobes are responsible for encoding processes.
• These processes help identify an item as familiar, as opposed to recollecting previously seen items.
• Perirhinal cortex activity increases with increased recognition confidence (familiarity), per Ranganath's 2004 research.
• The Hippocampus is responsible for recognition, based on recollection of information, while perirhinal cortex supports recognition, based on familiarity.
• These findings also apply to retrieval (Montaldi et al., 2006).

Wheeler et al. (2000)

• Conducted research on neural activity related to viewing pictures/sounds, and recalling pictures/sounds.
• There is evidence of information flowing out from the hippocampus, reactivating the original cortical areas that provided the input during encoding.

Frontal Cortex in Encoding and Retrieval

• The frontal cortex is shown to have a role in encoding and retrieval.
• Cabeza's theory states encoding involves the left frontal cortex, and retrieval involves the right frontal cortex.
• Kelley's theory states the left frontal cortex is involved in encoding/retrieval of linguistic information; the right frontal cortex, involving encoding/retrieval.

Memory Consolidation

• Memory consolidation stabilizes memory over time after it’s first acquired.
• Memory consolidation consists of rapid (hippocampus-dependent) and slower permanent consolidation processes.
• Electroconvulsive therapy (ECT) and head injury can cause retrograde amnesia.
• ECT and head injuries are more likely to affect recently learned items, suggesting rapid consolidation is most prone to disruption.

Limbic Scars

• Childhood maltreatment is associated with reduced hippocampal volume (n = 145). (Dannlowski et al., 2012, Biological Psychiatry)
• The hippocampus is highly susceptible to stress, including high expression of glucocorticoid receptors.

Cellular Basis of Learning and Memory

• In 1949, Donald Hebb suggested that learning has a biological basis.
• Hebb's theory is summarized as "cells that fire together wire together".
• In 1894, Santiago Ramon y Cajal suggested memory is stored via growth in new connections between neurons.
• Hebb's law indicates that the synapse will be strengthened if a synapse is active when a postsynaptic neuron is active.
• Bliss and Lømo (1973) stimulated axons in the rabbit hippocampus, increasing the magnitude of downstream neuron action potentials.
• This phenomenon is referred to as Long-Term Potentiation (LTP).
• Long-term Potentiation (LTP) in the hippocampus occurs when Bliss and Lomo stimulated the axons of the performant pathway with burst of pulses.
• This leads to an increase in EPSPs in the dentate gyrus granule cells, per Gazzaniga et al. (2014).

Molecular Mechanisms of LTP

• NMDA (N-methyl-D-aspartate) receptors are blocked by magnesium and open when glutamate binds and the membrane is depolarized.
• An open ion channel allows calcium ions to enter the cell.
• Calcium acts as an intracellular messenger, influencing enzyme activities and synaptic strength.

Neurobiology of Long-Term Memory

• Long-term memory lasts days to years.
• The medial temporal lobes (hippocampus and parahippocampal gyrus) are important.
• Cellular mechanisms of long-term memory consists of long-term potentiation.
• "Cells that fire together wire together" is a good summary.
• The NMDA receptor plays an important role.