What are the components of the limbic system?
- Amygdaloid nuclei
- Hippocampal formation
- Olfactory bulb, tract, cortex
- Limbic cortex
- Septal nuclei
- N. accumbens
- Orbitofrontal cortex
- Median dorsal (DM) thalamic nucleus
- Ventral parts of basal ganglia also associated
- NOTE: originally called rhinencephalon (olfaction), but now considered the "emotional brain"
What is the role of the limbic system?
- Circuits concerned with both control of EMOTIONS (amygdala especially) and COGNITIVE (more hippocampal) functions
- NOTE: components of the circuit actually constitute a large proportion of the brain (no specific list)
What is the primary function of the amygdaloid nuclei? Where are they located anatomically?
- FUNCTION: control of emotions
1. Autonomic function
- Note location in attached figure: in temporal lobe, just anterior to the hippocampal formation (basically at level of anterior termination of inferior horn of lateral ventricle)
What does the amygdala consist of?
- Several nuclei: not all functionally related (in anterior part of the temporal lobe)
- Olfaction, emotions, autonomics, learning and memory
What are the 3 main groups of amygdaloid nuclei?
- CORTICOMEDIAL (Co): olfactory part
- CENTRAL (C): principal output nucleus with striatum-like structure -> important for autonomic control
- BASOLATERAL (BL): principal input nucleus assoc w/neocortex and thalamus
Describe the relative positions of the three amygdaloid nuclei.
- CORTICOMEDIAL: anterior, medial, and cortical nuclei
- CENTRAL: close relationship with the striatum -> principal cell type is medium spiny GABAergic neuron, and high density of DA-containing axons (and DA concentration)
- BASOLATERAL: basal, lateral, and accessory basal nuclei -> largest, best differentiated nucleus in humans
1. Principal neuron pyramidal cell (glutamatergic), similar to neocortex and hippocampus
What are the major connections of the amygdaloid nuclei?
- CORTICOMEDIAL: main inputs from the olfactory bulb -> this is the olfactory amygdala
1. Other inputs come from parabrachial nucleus (taste processing) and medial dorsal (MD) and ventromedial (VM) thalamus
2. Primary output to hypothalamus (via stria terminalis) and back to olfactory bulb
- CENTRAL NUCLEUS: receives major inputs from basolateral nuclei of amygdala and hypothalamus
1. Principal output is to brainstem, hypothalamus (regulates autonomic systems), and striatum and midline (non-specific) thalamic nuclei (arousal)
- BASOLATERAL: receives inputs from many areas of association cortex and olfactory cortex
1. Main output to central nucleus of the amgydala, but also project to the hypothalamus, and many areas of cortex and thalamus (esp. DM)
2. Projections from basolateral to the entorhinal cortex (ERC) and subiculum are only association bt amygdaloid nuclei and hippocampal formation
Describe the inputs and outputs, and main function of the central nucleus of the amygdala.
- See image for primary inputs/outputs
- MAIN FUNCTIONS: autonomic control (BP, HR), arousal, and subjective experience
Describe the inputs and outputs of the basolateral nucleus of the amygdala.
- Inputs from many parts of the cortex (association cortex primarily), thalamus, and hippocampal formation -> includes highly processed sensory info
- Main output to central nucleus of the amygdala, but other strong outputs to PFC and reward circuits in the nucleus accumbens and striatum
What happens experimentally in the case of stimulation or lesions of the amygdala?
- Electrically stimulated = arrest reaction (fear reaction)
1. In cats, stimulated rage -> suggests some sort of link to emotions (fear, anxiety, anger)
- Lesions freq disturb emotional and/or social behavior in animals -> amygdala crucial for regulating emo and social behavior
How do amygdaloid lesions affect monkeys?
- Lead to an animal that is hypersexual and tame or placid (natural state of these animals is to be aggressive and uncomfortable around people)
- They do NOT show fear to threatening objects (e.g., snake or other predator)
- Feeding disorders (BL lesion = hyperphagia; CN lesion = hypophagia)
- Animals with bilateral amygdaloid lesions are very oral – they put everything in their mouth
What is Kluver-Bucy syndrome?
- Bilateral loss of the anterior temporal lobe
- Rare in human pts
- Pts are hypersexual, overly tame or placid, exhibit hyperphagia, are hyperactive, and express psychic blindness (do not recognize emo content of facial expressions)
What is the purpose of this illustration?
- Pt w/Urbech-Wiethe disease (calcification of neural tissue) in bilateral anterior temporal lobes
- Pt much worse at recognizing faces expressing fear than control pts (social implications: if you cannot recognize ppl's emos, you can't behave appropriately towards them)
- When instructed to draw faces showing the various emotions, pt did ok, but for fear she drew the baby shown in the image
- TAKEAWAY: amygdala (esp. basolateral) thought to be the executor of emo behavior, perhaps esp. fear
How is the BL nucleus involved in fear learning?
- It is ideally placed (bt cortical sensory inputs and outputs to hypothalamus and central nucleus) to integrate emotional behavior & sensory experience
- Important nucleus for the emotional component of learning and memories
- Integration of emotional and social behavior
Where is the hippocampus located?
- Hippocampal formation is a telencephalic structure located in the TEMPORAL LOBE
- Anteriorly, it relates to the amygdaloid nuclei
Describe the anatomical relationship of the hippocampal formation and the surrounding structures.
- Proximal to the inferior horn of the lateral ventricle (hippocampal formation is medial and superior to the ventricle) and amygdaloid nuclei (mostly posterior and inferior to the amygdala)
- Alveus is collected axons of hippocampal pyramidal cells -> these fibers collect and form the fimbria, which in turn becomes the fornix (main white matter to and from hippocampal formation)
- IMAGE: yellow arrow points to the hippocampal formation
What do you see here (thick blue line and yellow arrow)?
- Coronal section
- Parahippocampal gyrus indicated by thick blue line
- Yellow arrow points to the fimbria as it leaves the fornix (posterior and medial part of hippocampal formation)
How is the hippocampus related to the fornix?
- Alveus -> fimbriae -> fornix
- Note the parts of the fornix (crura, body, column), the mammillary bodies (hypothalamus), anterior nucleus of the thalamus (projects to cingulate gyrus), and the mammillothalamic tract also in the attached image
What are the major components of the hippocampal formation?
- Major components: subiculum, CA fields (CA1, CA2, CA3, CA4), and the dentate gyrus -> the CA fields are considered the hippocampus proper
- IMAGE: coronal section of temporal lobe showing the fimbria (red arrow)
- NOTE: much of the gray mater in parahippocampal gyrus entorhinal cortex (mesocortex), w/characteristic deep white mater and superficial gray matter
What are the 2 major input pathways to the hippocampal formation?
- Perforant pathway from lateral entorhinal cortex (RED)
- Alvear pathway from the medial entorhinal cortex (BLACK)
- NOTE: fine cell bodies of granular cells in dentate gyrus; in this view, cells arrayed in a reversed C-like pattern, w/opening facing end of CA field (CA4 end)
What are the principal cells in the entorhinal cortex, subiculum, CA fields, and dentate gyrus?
- PYRAMIDAL CELLS (glutametergic, excitatory): principal cells in the ERC, CA fields (hippocampus proper), and subiculum
- SMALL GRANULE CELLS (glutamatergic, excitatory): principal cells of dentate gyrus
- NOTE: image shows Golgi-filled neuron types in each part of the hippocampal formation (fornix at bottom); this is the medial aspect
How many layers do the various parts of the hippocampal formation have?
What are the main input/output of the dentate gyrus?
- Cellular distributions of all hippocampal formation subregions highly laminar and regular
- CA fields, subiculum = 3-layered allocortex with molecular (relatively cell poor), pyramidal (cell bodies of principal, pyramidal neurons), and polymorphic layer (many cell types; interneurons)
- Dentate gyrus = also 3-layered (molecular, granular, polymorphic), but main difference is the principal cells are granule cells rather than pyramidal cells
1. Main INPUT to dentate gyrus is via entorhinal cortex, and its main OUTPUT is to CA3
What is the trisynaptic circuit?
- Canonical hippocampal circuitry = trisynaptic circuit:
1. Main input to hippocampal formation is an excitatory (glutamatergic) projection from entorhinal cortex to granule cells (ERC -> DG)
2. Granule cells in dentate gyrus project (excitatory, glutamatergic) to CA3 pyramidal cells (DG -> CA3)
3. CA3 pyramidal cells project (excitatory, glu) to CA1 pyramidal cells (CA3 -> CA1)
What are the major inputs to CA fields?
- Perforant and alvear paths (see image)
- Trisynaptic circuit (perforant path):
1. ERC pyramidal cells -> DG
2. DG (granule cells) -> CA3 via mossy fibers (esp. secure and powerful synapse)
3. CA3 pyramidal cells -> CA1 via Schaeffer collaterals
- Alvear path: ERC -> CA1
- Both CA1 and CA3 receive inputs and project to the septal nuclei and contralateral hippocampus (via commissural fibers)
- All of these areas receive modulatory inputs from brainstem nuclei containing NE, serotonin, Ach, etc.
Besides the trisynaptic circuit, do hippocampal areas project anywhere else? What are the chief inputs and outputs for the hippocampal formation?
- Most hippocampal areas project to multiple other areas (besides main trisynaptic circuit)
1. Ex: ERC -> DG as well as CA3 (and to a lesser extent, CA1); similarly, CA1 -> subiculum, as well as ERC
- Almost all INPUTS to the hippocampal formation come via the entorhinal cortex (ERC or EC)
- Almost all OUTPUTS from the hippocampal formation are via the subiculum
Describe this pathway. Note the anatomical locations of the relevant structures.
- ERC -> dentate granule = perforant path
- Dentate granule -> CA3 pyramidal = mossy fibers
- CA3 pyramidal -> CA1 pyramidal = Schaffer collaterals
From where does the ERC receive info? Where does the subiculum send info?
- ERC (gateway to hippocampall formation; red square) receives INPUT from widespread areas of cortex, thalamus, and brainstem -> hippocampus receives highly processed info about most of our experience
- Virtually all OUTPUT of hippocampal formation is via the subiculum (green square) -> projects widely throughout cortex (potential substrate for storage of long- term declarative memory)
What is this?
- Golgi-stained pyramidal cell in hippocampus
- Principal cells of the CA fields and subiculum are pyramidal neurons (attached image here too; note spines and apical dendrite)
- Note the numerous dendritic spines (primary site of excitatory inputs)
How can epilepsy damage the hippocampus? Why?
- Hippocampal pyramidal neurons (esp. CA1) highly susceptible to many insults, incl epilepsy & ischemia
- Bc of prevalence of excitatory neurons and their interconnections, hippocampal formation (and ERC) are highly susceptible to seizures
- As in neocortex, < numerous GABAergic INH inter-neurons play important role in regulating excitability and synchrony of activity in the hippocampus
- IMAGE: different stains of sections of hippocampal formation from epileptic pt w/hippocampal sclerosis -> note the loss of neurons in DG and all CA ammon’s horn fields, esp. CA1
- NOTE: amygdala and neocortex also highly susceptible to seizures (temp. lobe epilepsy)
How can Alzheimer's affect the hippocampus?
- Severe loss of cells and brain shrinkage in late stage Alzheimer's -> hippocampal pyramidal cells appear to be especially sensitive to this disease
- Loss of hippocampal neurons may be the basis for loss of memory, a hallmark of the disease