Hippocampus Flashcards
What is the hippocampus?
involved in memory formation, spatial navigation, and emotional regulation. It is part of the limbic system and is located in the medial temporal lobe of the brain. Structurally, the hippocampus has a complex, highly organized architecture that supports its functions in information processing and synaptic plasticity.
Describe the strucutre of the hippocampus
Cornu Ammonis (CA) Regions
The hippocampus is subdivided into four CA regions (CA1–CA4), which are functionally and structurally distinct:
CA1: Plays a critical role in memory consolidation and spatial navigation.
CA2: A relatively small but unique region, involved in social memory.
CA3: Important for pattern separation and associative memory.
CA4: Embedded within the dentate gyrus and involved in processing inputs.
Dentate Gyrus (DG)
The dentate gyrus is the main input region of the hippocampus.
It contains granule cells that receive excitatory input from the entorhinal cortex via the perforant pathway.
It plays a role in neurogenesis (the birth of new neurons), which is rare in the adult brain.
Subiculum
The major output structure of the hippocampus.
Connects the hippocampus to the entorhinal cortex, which projects information back to the neocortex for further processing.
Discuss the cells that make up the hippocampus
The hippocampus is composed of several distinct layers, primarily made up of excitatory pyramidal neurons (in CA regions) and granule cells (in the dentate gyrus). These layers include:
Stratum Pyramidale
Contains densely packed pyramidal neurons, which are the principal excitatory cells.
These neurons are involved in long-term potentiation (LTP), a process essential for learning and memory.
Stratum Radiatum and Stratum Lacunosum-Moleculare
These layers contain dendrites of pyramidal neurons and incoming axons that form synaptic connections.
Stratum Oriens
Contains basal dendrites of pyramidal neurons and inhibitory interneurons that modulate hippocampal activity.
Molecular Layer (Dentate Gyrus)
Receives inputs from the entorhinal cortex and projects to CA3.
What is the trisynaptic circuit
The hippocampus is organized into a trisynaptic circuit, which is fundamental for its role in memory processing:
Perforant Pathway
Inputs from the entorhinal cortex synapse onto granule cells in the dentate gyrus.
Mossy Fiber Pathway
Granule cells in the dentate gyrus project excitatory axons (mossy fibers) to pyramidal neurons in CA3.
Schaffer Collateral Pathway
CA3 pyramidal neurons send axons to CA1 pyramidal neurons.
CA1 to Subiculum and Entorhinal Cortex
CA1 projects information to the subiculum, which then connects back to the entorhinal cortex and other cortical areas.
What is the function of the hippocampus
Memory Formation: The hippocampus is critical for converting short-term memories into long-term memories.
Spatial Navigation: Place cells in the hippocampus fire in response to specific spatial locations, forming a cognitive map.
Neurogenesis: The dentate gyrus is one of the few brain regions where adult neurogenesis occurs, contributing to learning and memory.
Neurodevelopmental and Neurodegenerative Disorders: The hippocampus is affected in conditions such as Alzheimer’s disease, epilepsy, and schizophrenia.
Describe the memory formation in the hippocampus
Memory Formation and Consolidation
One of the primary functions of the hippocampus is to facilitate the conversion of short-term memories into long-term memories, a process known as memory consolidation.
Hippocampal Role in Declarative Memory
Declarative memory (explicit memory) includes episodic memory (events, experiences) and semantic memory (facts, knowledge).
Information first enters the entorhinal cortex, which relays sensory input to the hippocampus through the perforant pathway.
The hippocampus then processes and strengthens these memories via synaptic plasticity, particularly through long-term potentiation (LTP).
The Trisynaptic Circuit in Memory Processing
The hippocampus follows a trisynaptic circuit to process and transmit memory-related information:
Perforant Pathway: Inputs from the entorhinal cortex reach the dentate gyrus, where initial processing occurs.
Mossy Fiber Pathway: Granule cells in the dentate gyrus send projections to CA3 pyramidal neurons.
Schaffer Collateral Pathway: CA3 pyramidal neurons send excitatory signals to CA1, which then transmits processed information to the subiculum and back to the entorhinal cortex.
Cortical Storage: The hippocampus eventually transfers long-term memories to the neocortex, particularly the prefrontal cortex.
Hippocampal-Dependent Memory Formation
The hippocampus is essential for new memory encoding but does not permanently store memories. Instead, it acts as a relay station that helps consolidate memories before transferring them to other brain regions for long-term storage.
Damage to the hippocampus, such as in Alzheimer’s disease, leads to severe anterograde amnesia (inability to form new memories).
Describe neurogenesis and learning that occurs in the hippocampus
- Neurogenesis and Learning
The dentate gyrus is one of the few brain regions where adult neurogenesis occurs.
New neurons integrate into hippocampal circuits, playing a role in learning, pattern separation, and memory flexibility.
Neurogenesis is modulated by factors like exercise, enriched environments, and stress.
Describe the emotional regulation and stress response in the hippocampus
The hippocampus is involved in emotional processing and stress regulation through its connections with the amygdala and hypothalamus.
Hippocampus-Amygdala Interaction
The hippocampus and amygdala work together in memory formation, particularly emotionally charged memories.
Emotional memories, such as those associated with fear or reward, are strengthened by interactions between the hippocampus and amygdala.
Regulation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis
The hippocampus contains glucocorticoid receptors that regulate the body’s response to stress.
It provides negative feedback to the hypothalamus, helping to suppress excessive release of cortisol.
Chronic stress can lead to hippocampal shrinkage, impairing memory and increasing susceptibility to psychiatric disorders such as depression.
Has electrophysiology been done onthe Ogg1 mice
What are exmaples of tests to measure hippocampal dependent function
earning, memory, and spatial navigation.
a) Morris Water Maze
A widely used test to measure spatial memory in rodents.
Mice or rats must find a hidden platform in a water pool, relying on hippocampal place cells.
b) Radial Arm Maze and T-Maze
Used to assess working memory and decision-making.
Tests hippocampal involvement in remembering previous choices.
c) Novel Object Recognition (NOR)
Measures recognition memory, which depends on hippocampal function.
d) Contextual Fear Conditioning
Examines hippocampus-dependent associative learning by pairing an aversive stimulus (e.g., a mild shock) with a specific context.
Impact of Prenatal Alcohol Exposure on Hippocampal Development
Prenatal alcohol exposure (PAE) can have profound effects on the developing hippocampus, leading to long-term cognitive and behavioral deficits. The hippocampus is particularly vulnerable to ethanol-induced neurotoxicity, as it undergoes critical periods of neurogenesis, differentiation, and synaptogenesis during gestation. PAE disrupts these processes, resulting in structural, functional, and molecular abnormalities that contribute to neurodevelopmental disorders such as fetal alcohol spectrum disorders (FASD).
- Structural Alterations in the Hippocampus
PAE leads to significant changes in the size, cellular composition, and connectivity of the hippocampus.
a) Reduced Hippocampal Volume
Human Studies: MRI studies in children with FASD show reduced hippocampal volume, particularly in the CA1 and dentate gyrus (DG).
Animal Studies: Rodent models of PAE demonstrate hippocampal shrinkage, with reduced cell numbers and impaired dendritic complexity.
b) Disrupted Neurogenesis in the Dentate Gyrus
The dentate gyrus is a major site of neurogenesis, particularly in late gestation and early postnatal life.
PAE reduces the proliferation of neural progenitor cells, leading to fewer granule cells in the DG, impairing memory function.
c) Deficits in Synaptic Connectivity
PAE disrupts the formation of hippocampal circuits, including:
Fewer synaptic connections in the CA1 and CA3 regions.
Reduced dendritic spine density, leading to weakened synaptic transmission.
Impaired Schaffer collateral pathway function (CA3 to CA1 connectivity).
d) Hippocampal Asymmetry
Studies suggest that PAE affects the left hippocampus more than the right, which may contribute to verbal memory deficits observed in FASD individuals.
2. Functional Deficits in Memory and Learning
PAE affects hippocampal-dependent cognitive functions, including memory and spatial navigation.
a) Impaired Spatial Memory and Navigation
Morris Water Maze (MWM) studies in rodents show that PAE-exposed animals take longer to locate the hidden platform, indicating hippocampal dysfunction.
Place cell activity in the hippocampus is reduced, affecting spatial memory.
b) Deficits in Long-Term Potentiation (LTP)
LTP, the molecular basis of learning and memory, is significantly reduced in PAE-exposed hippocampi.
Altered NMDA receptor and AMPA receptor function contributes to impaired synaptic plasticity.
c) Working Memory Deficits
PAE disrupts prefrontal cortex-hippocampus interactions, leading to impairments in working memory tasks like radial arm maze and T-maze tests.
