Limbic System (Week 5--Houser)

Question 1

Where are the hippocampus and limbic system?

Answer 1

Medial parts of the temporal lobe

Question 2

3 C-shaped structures and pathways of the limbic system

Answer 2

1) Limbic association cortex: cingulate and parahippocampal gyri
2) Hippocampus and fornix
3) Amygdaloid complex and stria terminalis

Question 3

Limbic cortical areas

Answer 3

Medial orbital gyri of frontal lobe

Cingulate gyrus of frontal and parietal lobes

Parahippocampal gyrus of temporal lobe

All receive input from higher order sensory and association areas

Question 4

How is the medial prefrontal cortex related to the limbic system?

Answer 4

Can influence various cortical and subcortical parts of the limbic system:

Cingulate gyrus

Hypothalamus

Dorsal thalamus

Amygdaloid complex

Some brainstem nuclei

Question 5

What structures are in the medial part of the temporal lobe?

Answer 5

Amygdala

Hippocampus

(both underneath the parahippocampal gyrus!)

Question 6

Parahippocampal gyrus

Answer 6

Continuation of cingulate gyrus on inferior surface of the brain

Cortex of parahippocampal gyrus includes subiculum and entorhinal cortex (both functionally related to hippocampus)

Rostrally, parahippocampal gyrus expands to form uncus (amygdala and anterior part of hippocampus underlie the uncus)

Question 7

Diverse functions of the limbic system

Answer 7

Emotion

Memory

Olfaction

Control of visceral function

Question 8

Papez circuit

Answer 8

Outdated, but a good model

Mammillary body –> anterior thalamic nucleus –>cingulate gyrus –> cingulum –> hippocampus –> hippocampus and subiculum –> fornix –> mammillary body

Question 9

Amygdala anatomy

Answer 9

Collection of several distinct nuclei, so called amygdaloid complex

In temporal lobe just beneath cortex of uncus (or parahippocampal gyrus!), immediately rostral to hippocampal formation

Question 10

3 major divisions of amygdaloid complex

Answer 10

Don’t need to know

Basolateral nuclei: largest group; connections with cerebral cortex, particularly sensory association areas, limbic association cortex (cingulate cortex, orbital and medial prefrontal cortex), and thalamus (MD nucleus); general function = emotion/experience

Central nuclear group: connections with brainstem and hypothalamic regions that include viscerosensory areas such as the nucleus of the solitary tract and autonomic nuclei such as the dorsal motor nucleus of the vagus; general function = visceral control

Medial group: connections with olfactory bulb, olfactory cortex and hypothalamus; general function = olfaction

Question 11

Efferent pathways of the amygdala

Answer 11

Stria terminalis: from medial group to parts of hypothalamus and septal areas

Ventral amygdalofugal system: diffuse but connects frontal cortex to brainstem

Interconnections among amygdaloid nuclei: connect cortical regions that provide highly processed sensory info (sensory association areas) with hypothalamic and brainstem regions that serve as effector systems

Question 12

Function of amygdala

Answer 12

Sensory events connected to emotional significance

Emotion-related aspects of learning

Learning about fearful stimuli

Evaluating the emotional significance of events in the environment

Question 13

Overview of function of hippocampal formation

Answer 13

Important role in memory

Bilateral damage causes loss of ability to consolidate short-term memory to long-term memory

Spatial memory

Question 14

3 regions of hippocampal formation

Answer 14

1) Dentate gyrus
2) Hippocapmus (Ammon’s Horn or Cornu Ammonis)
3) Subiculum

Question 15

Cells of the dentate gyrus vs. cells of the hippocampus

Answer 15

Granule cells major cell of dentate gyrus

Pyramidal cells major cell of hippocampus

Question 16

3 layers of cells of the dentate gyrus

Answer 16

1) Molecular layer = dendritic layer
2) Granule cell layer = cell body layer
3) Polymorph layer/hilus = axonal layer

In general, dendrites of granule cell layer extend into relatively neuron-free region above granule cell layer and layer of polymorph cells below or within granule cell layer

Question 17

3 layers of hippocampus

Answer 17

1) Stratum radiatum = dendritic layer
2) Pyramidal cell layer = cell body layer
3) Stratum oriens = axonal layer

Interneurons in each layer but most prominent within or immediately below granule cell/pyramidal cell layers; many of the interneurons are basket cells that use GABA and inhibit input to cell bodies of principal cells

In general, dendrites of pyramidal cell layer extend into relatively neuron-free region above pyramidal cell layer and layer of polymorph cells below or within pyramidal cell layer

Question 18

Basket cells

Answer 18

One type of GABA interneuron

Inhibit cell bodies of principal cells of dentate gyrus (granule cells) and hippocampus (pyramidal cells)

Neuronal cell bodies and axon terminals in dentate gyrus

Question 19

Trisynaptic circuit through hippocampal formation (most classical hippocampal pathway)

Answer 19

Info from all over the cortex –> entorhinal cortex –> across hippocampal fissure (perforated path) –> dentate gyrus (and also small input to hippocampus) –> granule cells send axons to CA3 of hippocampus ONLY –> pyramidal cells send projection to CA1 field (but some from CA3 leave hippocampus via fornix) –> most sent to subiculum –> entorhinal cortex –> cortical association areas

Summary: entorhinal cortex through perforant path to dentate gyrus –> mossy fibers to CA3 –> Schaffer collaterals to CA1 –> subiculum –> entorhinal cortex

Question 20

Links in hippocampal pathways

Answer 20

Perforant path: major projection from entorhinal cortex to dentate gyrus and hippocampus; crosses or “perforates” hippocampal fissure to reach dentate

Mossy fibers: axons of granule cells of dentate gyrus that have large, characteristic terminals that contact CA3 neurons

Schaffer collaterals: axon collaterals from CA3 neurons to CA1

Question 21

Where does the hippocampus send info via fornix?

Answer 21

Hippocampus sends info to mammillary bodies and septal region through the fornix

Question 22

What NT is used in the basic hippocampal circuitry fron entorhinal cortex –> dentate gyrus –> CA3 –> CA1?

Answer 22

Glutamate (excitatory) used in this circuitry!!

Mossy fibers which project from dentate gyrus to CA3 also contain high levels of zinc and other neuropeptides

Question 23

Where is acetylcholine used?

Answer 23

ACh is major NT of neurons from septal nuclei to hippocampal formation; part of group of cholinergic neurons in basal forebrain; remember basal nucleus of Meynert project to all areas of cerebral cortex

Choliergic neurons in septal nuclei project to hippocampal formation through fornix

Question 24

Why is cholinergic innervation of the hippocampus special?

Answer 24

1) Cholinergic neurons that innervate hippocampus (from septal nuclei, through fornix) are severely depleted in Alzheimer’s disease
2) Nerve growth factor (NGF) has been found to influence survival of cholinergic neurons in CNS

Question 25

What NT is used by intrinsic neurons within the hippocampus and dentate gyrus?

Answer 25

**GABA** used by many **intrinsic** **neurons** (one example is **basket** **cells**) (There are also GABA neurons in septum that project to hippocampus)

Question 26

Which neuropeptides are found in interneurons in hippocampus?

Answer 26

Somatostatin, CCK, VIP Co-localized with other neuroactive substances such as GABA

Question 27

What diseases show selective vulnerability of neurons in hippocampal formation?

Answer 27

**Ischemia**: **CA1** field of hippocampal formation; excitotoxicity involved (get loss of short term memory) **Temporal** **lobe** **epilepsy**: **CA1** field and hilus of **dentate** **gyrus**, and **CA3** field; hippocampus becomes shrunken (**hippocampal** **sclerosis**); granule cells of dentate gyrus and CA2 field are spared **Alzheimer's disease**: **entorhinal** **cortex** and **CA1** field; however other brain regions involved, such as cerebral cortex and basal forebrain

Question 28

Neurogenesis in the adult brain

Answer 28

Occurs in **dentate** **gyrus** and **subventricular zone** New granule cells generated from dividing progenitor cells: new neurons generated near base of granule cell layer, differentiate, extend axons and are incorporated into existing circuitry of hippocampus **Environmental** **factors** and **stimulation** can influence rate of neurogenesis

Question 29

Do axons of the CNS regenerate?

Answer 29

**Not over long distance**, and is limited However, **axonal** **reorganization** or **"sprouting" does occur!**

Question 30

Axonal sprouting/reorganization

Answer 30

Undamaged neurons form **new synaptic connections** in response to either loss of normal targets or deafferentation of nearby neurons **Axon** **collaterals** of remaining neurons occupy **synaptic sites that have been vacated** by damaged neurons

Question 31

Reorganization of mossy fibers of dentate gurys in patients with temporal lobe epilepsy

Answer 31

**Normally**, mossy fibers confined to **hilus** **of** **dentate** **gyrus** and **CA3** field, but in **epilepsy** patients, putative **mossy fibers** or collaterals **occupy inner part of molecular layer** 1) **Hilar** (polymorph, PM) neurons normally innervate **inner molecular layer** of dentate gyrus 2) Hilar neurons (and CA3 neurons) **depleted** in epilepsy patients, so granule cells lost major sites of termination 3) Loss of hilar neurons led to **vacated synaptic sites** in inner molecular layer 4) **Granule cells** send axon collaterals **into inner molecular layers** and **innervate vacated synaptic sites** --\> leads to **hyperexcitability**, increased **synchronization** of firing of granule cells, epileptiform activity

Question 32

Do similar types of neuronal reorganizaton occur in other neurological disorders?

Answer 32

Yes! Just not shown in humans yet **Spinal shock to hyperreflexia** after **spinal cord injury** may be explained by axonal sprouting **Spasticity after stroke** may be explained by reorganiation of axons from remaining neurons Also axonal reorganization could have **beneficial** effects and contribute to recovery of function in neurological disorders

Question 33

Nucleus accumbens

Answer 33

Located **rostrally** in the brain, where **caudate and putamen meet** at the bottom (is in the "ventral striatum") **Ventral tegmental area** of the substantia nigra projects up to nucleus accumbens using **dopamineric** neurons Implicated in the reward system

Question 34

Regions involved in emotion

Answer 34

**Orbital and medial prefrontal cortex** (**ventral** **basal** **ganglia**) **Amygdala** **MD nucleus of thalamus**

Question 35

What happens if you lose the amygdala on both sides?

Answer 35

Can't recognize fearful expressions

Question 36

Amygdala and emotional response

Answer 36

Receives wide variety of sensory inputs Strong connections with cerebral cortex and hypothalamus Involved in emotion-related aspects of learning (if something is good or bad; strong emotion --\> strong memories) Involved in associating sensory experience with emotional significance

Question 37

Flow of information into the hippocampus--where does this info come from?

Answer 37

Information comes from many areas of the **cortex** into the **cingulate gyrus** --\> through fibers of the **cingulum** --\> feeds into **entorhinal cortex**

Question 38

What are CA1, CA2, CA3?

Answer 38

Just different **regions** of the **hippocampus**

Question 39

What do we use to control the very excitatory hippocampal pathway that uses glutamate only?

Answer 39

**GABAergic interneurons** (one example is **basket cells**) Also **cholinergic** input is important for controlling the system

Question 40

Where exactly are the septal nuclei?

Answer 40

Gray matter area along the **base of the septum pellucidum** (between lateral ventricles)

Question 41

In patient RB who had global ischemia, what happened?

Answer 41

**CA1** cells were damaged (they were selectively vulnerable) Loss of these CA1 cells **interrupted** the hippocampal **loop** and that caused deficit where patient had anterograde amnesia (couldn't form new memories)

Question 42

How could excitotoxicity kill cells?

Answer 42

Excitotoxicity is abnormal excessive accumulation of glutamate that can "excite" neurons to death NMDA receptors probably involved here because they can let too much **Ca2+** in

Question 43

Hippocampal sclerosis

Answer 43

Shrunked hippocampus Gliosis Extensive cell loss but selective (hilus of dentate, CA3, CA1) Preservation of granule cells of dentate gyrus and CA2 Example of selective vulnerability

Question 44

What can affect neurogenesis?

Answer 44

**Increased** **neurogenesis**: severe acute seizure activity, exercise, SSRIs, enriched environment **Decreased neurogenesis**: chronic stress

Question 45

What happens when granule cells are interconnected?

Answer 45

Normally, **granule** **cells** are not interconnected--they just form their own little path out If they lost places they need to project (hilar cells) and lost things that should innervate them (hilar cells), they form **interconnections** and **innervate** **each** **other** Consequences: **synchronous** firing of granule cells; lose **inhibitory interneurons** that usually control this region