Hippocampus

Question 1

what is the temporal lobe for?

Answer 1

declarative memory

Question 2

what are the three areas of temporal lobe and their function?

Answer 2

• Amygdala: Important part of the limbic system-Critical for emotional memory (a type of non-declarative memory)
• Hippocampal formation: Large component of the temporal lobe that includes the hippocampus and various tightly connected regions of the underlying temporal cortex. The fornix is the main efferent pathway of the hippocampal formation. Plays a critical role in declarative long-term memory. A bilateral lesion of part of this brain region results in amnesia. The severity of the memory deficits is directly correlated with the extent of the lesion.
• Mammillary Bodies: Main target of hippocampal projections. A selective lesion induces anterograde amnesia.

Question 3

components of the hippocampal formation in human?

Answer 3

Entorhinal cortex
Dentate gyrus
Hippocampus (CA1, CA2, CA3)
Subiculum

additional temporal lobe cortice connected with:
parahippocampal cortex
perirhinal cortex

(check the graph for their location)

Question 4

where is the hippocampal formation of rodents?

Answer 4

In rodents, the hippocampal formation appears as an elongated structure extending in a C-shaped fashion from the septal nucleus rostrally, over and behind the diencephalon, to the temporal lobe caudoventrally. The long axis of the hippocampal formation is often referred to as the Septo(S)-Temporal(T) axis.

Question 5

anatomical subdivision of the hippocampal formation?

Answer 5

DG: dentate gyrus
PoDG: polymorphic layer of dentate gyrus
CA1, CA2, CA3
Fi: Fimbria

Question 6

anatomy of DG?

Answer 6

Mainly granule cells with spiny dendrites-Glutamatergic-Projection neurons to CA3. Also some GABAergic interneurons.

Question 7

anatomy of PoDG?

Answer 7

Large variety of glutamatergic and GABAergic neurons. Local connections within the DG.

Question 8

anatomy of CA1/CA2/CA3?

Answer 8

1. Main cell types are Pyramidal Cells-Glutamatergic-Spiny dendrites-Projection neurons to other hippocampal regions and outside the hipp. formation.
2. Main difference between CA1 and CA3 based on afferents. Pyramidal cells in CA3 are larger than in CA1
3. CA2: Small group of pyramidal cells between CA1 and CA3. Controversial area. Connectivity unclear.
4. Also various populations of GABAergic interneurons-Basket Cells, innervate cell bodies of Pyramidal neurons.

Question 9

anatomy of fimbria?

Answer 9

Axons of pyramidal cells en route to subcortical projections. Will form the fornix. Some afferents to the hippocampus also flow through this tract.

Question 10

what are the modulatory monoamine inputs to the HF and their function?

Answer 10

Brainstem monoaminergic inputs
1. Noradrenaline input
Arises from locus coeruleus;
Terminates mainly in dentate gyrus;
2. Serotonin input
Arises from the raphe nucleus;
Terminates mainly in dentate gyrus and part of the entorhinal cortex;
3. Dopamine input
Arises from the ventral tegmental area;
Very little innervation of the hippocampus and dentate gyrus;
Clusters of terminals in entorhinal cortex;

function: These inputs are involved in the modulation and fine- tuning of glutamatergic and GABAergic synaptic transmission in the hippocampal formation.

Question 11

what is the main target of Alzheimer’s disease?

Answer 11

the cholinergic septo-hippocampal pathway

Question 12

describe the septo-hippocampal tract

Answer 12

ACETYLCHOLINE is the main neuromodulator of the hippocampus.

Arises mainly from cholinergic neurons in the medial septum (MS) and Diagonal Band of Broca (VDB) located along the midline in the basal forebrain.

Terminates in all fields of the hippocampal formation.

Flows through the fimbria-fornix fiber track.

Cholinergic fibers of this pathway are among the first to degenerate in Alzheimer’s disease.

The septo-hippocampal projection is not exclusively made up of cholinergic fibers, GABAergic neurons in MS also project to the hippocampal formation.

Question 13

the anatomy of long-term memory storage?

Answer 13

High order association areas in the prefrontal, parietal and temporal cortex send information to the entorhinal cortex

The entorhinal cortex serves as the main entrance for this complex information to the hippocampus

The hippocampal formation provides reciprocal inputs to these cortical areas, which may represent routes for long term storage of cortical memory

Question 14

describe the trisynaptic pathway of the HF

Answer 14

All projections of this pathway use glutamate as neurotransmitter;
All projections arise from pyramidal cells except the mossy fiber pathway that originates from granule cells in the dentate gyrus;
All projections display long term potentation when stimulated at high frequency;
Many populations of GABAergic interneurons modulate activity of glutamatergic cells that give rise to these projections.

(check the picture in the slides)

Question 15

describe LTP

Answer 15

Persistent increase in synaptic strength (as measured by the amplitude of EPSP in a postsynaptic neuron) that can be induced rapidly by a brief BURST of spike activity in presynaptic afferents. The resulting potentiation can last several hours, even days???

LTP can be induced at all glutamatergic synapses of the hippocampal trisynaptic pathway, but the mechanisms involved differ from one synapse to the other (associative versus non-associative LTP)

The mechanisms that induce LTP are very complex and involve pre- and post-synaptic changes in synaptic transmission, intracellular calcium, and changes in the trafficking of post-synaptic glutamate ionotropic receptors

Question 16

LTP: a complex phenomenon that involves neurochemical

Answer 16

1. The mechanisms of induction and maintenance of LTP at various synapses in the CNS are very complex and, for many cases, remain controversial.
2. This example shows the proposed changes going on in the induction and maintenance of LTP at Schaffer collateral synapses on CA1 pyramidal neurons.
3. During normal, low-frequency, synaptic transmission glutamate acts on both NMDA and non-NMDA receptors, but the ions flow mainly through the AMPA receptors since the NMDA channels are blocked by Mg+2 at resting membrane potential.
4. During high frequency stimulation, 4 important events occur that induce LTP: 1) postsynaptic depolarization, 2) loss of Mg+2 block of NMDA receptors, 3) activation of NMDA receptors, 4) influx of Ca++ through NMDA receptors and 5) activation by Ca++ of several second messenger systems.
5. The mechanisms for the expression and maintenance of this LTP are controversial, but involve: 1) increased density of AMPA receptors at the synapse, 2) increased sensitivity of AMPA receptors through phosphorylation, and 3) possibly increased neurotransmitter release from the pre-synaptic terminal in response to release of nitric oxide from the postsyTnaptic neuron.

Question 17

dendritic spine: spines undergo complex changes in both shape and number over time after a novel experience or conditioning stimulus

Answer 17

1. After conditioning stimulus, increase neurotransmitter release from terminal and transient increase in postsynaptic intracellular calcium (Early phase of LTP)
2. Expansion of spine head, formation of new AMPA receptors. Increased size of the post-synaptic density. Accumulation of F-actin.
3. Several hours later, new spines are formed (late phase of LTP).
4. A similar sequence of events can occur when the stimulus leads to long-term depression (LTD) rather than LTP.
5. Initially, calcium is raised in the spine, neurotransmitter release is reduced , F-actin is converted to G-actin.
6. Elongation of spine, reduced communication with pre-synaptic terminal, shrinkage of spine head, spine pruning.

Question 18

what is the change of protein synthesis in spines that undergo LTP?

Answer 18

redistribution of polyribosomes from dendritic shafts into spines

experiment:

• Two hours tetanic stimulation-induced LTP in rat brain hippocampal slices
• 3D electron microscopic reconstruction of dendrites and spines from neurons located beneath the stimulating electrode.
• The number of spines with polyribosomes is significantly increased in spines that undergo LTP

Question 19

describe the experiment that shows that learning enhances adult neurogenesis in the DG

Answer 19

conclusion:
THE NUMBER OF BRDU-LABELED CELLS IN THE DENTATE GYRUS OF ANIMALS TRAINED TO LEARN THE HIPPOCAMPUS-DEPENDENT TASK IS MUCH HIGHER THAN IN THE DENTATE GYRUS OF ANIMALS TRAINED TO LEARN HIPPOCAMPUS-INDEPENDENT TASKS.

Question 20

three evidence that newly generated neurons in the DG receive functional synaptic inputs

Answer 20

(check the slides)

Question 21

three evidence that new neurons in the DG provide functional glutamatergic synapses to target hippocampal neurons

Answer 21

1. subpopulation of adult-born DG neurons (labeled with GFP) and their axonal projections to the CA3 region
2. the GFP-labeled mossy fiber terminals form synapses with the dendrites of CA3 pyramidal neurons
3. excitatory light-evoked synaptic response in CA3 neuron via optogenetics are blocked by glutamate antagonists

Question 22

experiment show that neurogenesis relate to some, but not all types of hippocampal-dependent learning

Answer 22

EXPERIMENTAL DESIGN: Adult rats treated with saline or methylazoxymethanol acetate (MAM), am antimitotic toxin that blocks neuronal proliferation, are trained in a spatial navigation task in which they have to use spatial cues to find a platform in the pool. The latency to find the platform is measured as an index of learning. This task needs an intact hippocampal formation to be performed

The MAM-treated rats perform as well as controls in this task.

CONCLUSION: NEUROGENESIS IN THE HIPPOCAMPUS IS ASSOCIATED WITH SOME, BUT NOT ALL TYPES OF HIPPOCAMPAL-DEPENDENT MEMORIES

Question 23

describe the connectivity of the mammilary bodies

Answer 23

1. Made up of two subdivisions, lateral and medial.
2. These two divisions receive afferents from different parts of the hippocampal formation.
3. Both parts are reciprocally connected with different subdivisions (Ventral and dorsal) of the Gudden’s tegmental nucleus, and project to different anterior thalamic nuclei via the mammilothalamic tract (see previous slide).

Question 24

describe Wernicke/Korsakoff’s Syndrome (WKS)

Answer 24

the mammilary bodies and anterior thalamic nuclei are degenerated in patients with WKS

WKS:
WKS is due to thiamine deficiency often associated with alcoholism;
Severe reduction in size of both mammilary bodies (MB-red outlines) and anterior thalamic (AP-green outlines) nuclei;
Reduced ability to learn new information i.e. ANTEROGRADE AMNESIA. Memory for past events is usually intact (remember events that happened 20 years ago, but cannot recall what they did during the last 10 minutes).

Question 25

what is one of the main neuropathological features of Alzheimer’s disease

Answer 25

senile plaques

• Plaques are found in the brains of elderly humans and animals (mammals/birds), not only in AD patient brains.
• The number of plaques increase with age.
• The number of plaques is higher in the brain of AD patients than in normal aged human.

Question 26

cellular pathology evidence on post-mortem examination of the brain of Alzheimer’s disease

Answer 26

Neurofibrillary tangles: Collections of abnormal aggregation on intraneuronal cytoskeletal elements.

Senile plaques: Extracellular deposits of an abnormal protein called BETA AMYLOID.
Degenerated neural processes. Increased density of astrocytes and microglia.

Diffuse loss of neurons: Hippocampal formation, neocortex, basal forebrain cholinergic neurons in medial septum and nucleus basalis of Meynert.

Question 27

genes related to Alzheimer’s disease

Answer 27

amyloid precursor protein
presenilin 1 and 2
apolipoprotein E

Question 28

describe the three trisynaptic pathway

Answer 28

perforant pathway: entorhinal cortex to dentate gyrus, associative LTP
mossy fiber pathway: dentate gyrus to CA3, non-associative LTP
Schaffer collateral pathway: CA3 to CA1, associative LTP

associative LTP: enhanced response to a group of weak neurons when pairing to a group of strong neurons; think of the classical conditioning

nonassociative LTP: does not depend on postsynaptic activity or other signals arrive close in time, but depends on a burst of brief, high-frequency activity at presynaptic level and consequent influx of calcium.