Lecture 14

Limbic System

• Limbic system encircles the upper portion of the brainstem and includes:
  
  • Olfactory Bulbs
    
  • Amygdaloid bodies
    
  • Cingulate Gyrus (in the medial side of the hemisphere at the top)
    
  • Parahippocampal Gyrus
    
  • Hippocampus (the internal gyrus that goes into the inferior horn of the lateral ventricle)
    
  • Fornix
    
  • Mammillary Bodies of the hypothalamus
    
  • Thalamic and Hypothalamic nuclei
    
• Much of the brain is 6 layers deep, but parts of it are 3 layers deep.
  
• 3 layer parts are the Allocortex.
  
• 6 layer parts are the Neocortex.
  
• Transition areas between the 3 and 6 layer portions that are called the Juxtallocortex, it has 4 to 5 layers.
  
• Papez Circuit proposed by Papez (1930's) – it started at the Hippocampus (the Hipppocampus is part of the Allocortex).  The only efferent outlet of the Hippocampus is the Fornix, and it conducts in one direction and sends everything to the mammillary bodies. 
  
  • Circuit starts at the Hippocampus (via the Fornix)  Mammillary bodies of Hypothalamus  Anterior nuclei of Thalamus  Cigulate gyrus  Parahippocampal gyrus  Hippocampus.
    
  • He believed that the hippocampus was where emotions were organized.
    
  • Today the hippocampus is studied for memory not for limbic system function.
    
• The Limbic System is part of the brain that is responsible for:
  
  • Seeking and capturing prey
    
  • Courtship
    
  • Copulation
    
  • Maternal and Paternal behavior
    
  • Emotional Responses
    
  • Aggressive as well as communal behavior
    
  • Fight or flight
    
  • Memory formation
    
• Copulation:
  
  • In men there are many social, psychological, or neo-cortical functions that are going into sexual behavior.
    
    • Typically when we discuss sexual behavior, we talk about lower mammalian species that don't have as many social and psychosocial input and only talk about the basic instincts that are being formed by the Limbic system
      
  • Gonadal hormones stimulate sexual behavior in both the male and the female.
    
    • Testosterone in male, Estrogens in female.
      
  • In Males and Female – Gonadal hormone levels are detected/monitored by the hypothalamus.
    
  • In virtually all mammalian species the male's sexual activity interest is continuous.
    
  • The female in mammalian species, sexual activity is controlled the Estrus cycle. The Estrus Cycle is controlled by relative levels of estrogen and progesterone (relative level is used b/c to compare relativity to own level – ex. when they are relatively high or low)
    
    • When Estrogen levels increase – female in heat – we call this Estrus
      
      • The female is receptive to sexual intercourse
        
    • When Progesterone is high – female is out of heat – we call this Diestrus.
      
  • Certain mammals stop cycling their Estrus Cycle because they do not want to have their babies in the winter time.
    
    • Deer who would give birth in January would have high death rates of fawns.
      
    • The Doe will go through an Anestrus period – they do not cycle at all.
      
      • We think that Anestrus is brought on by day length, and when the day get short Anestrus will set in
        
  • The female will copulate only during Estrus, which is just prior to ovulation
    
  • We don't have an Estrus cycle in human females, but we do have signs of it
    
  • Human females – exhibit more skin in public in the few days prior to their ovulation.
    
    • Human females exhibit more sexual activity just prior to ovulation, and this is when their estrogen level is the highest.
      
    • Vaginal secretions of the female include Pheromones, which are fatty acid chemical signalers, that can actually result in various unlearned behaviors (such as having sex or suckling the breast).
      
      • Males that sense the pheromones of the vagina will become more sexually aggressive.
        
      • Female secrets pheromones form her nipples and the baby can smell and it knows to suckle.
        
• Fear and Rage – are closely related emotions (ex. If you chase a dog it will run from you, but if you are in an alley the fear of the dog will quickly turn to rage)
  
  • Fear and rage are centered in both Hypothalamic nuclei and the Amygdaloid body.
    
    • If the Amygdaloid body is destroyed you will have an animal that is fearless and rageless.
      
    • Some of the Hypothalamic nuclei are calming centers – this is b/c if they are destroyed you can cause rage in the animal.
      
    • We can create rage by stimulating the Lateral Hypothalamus.
      

 
 

• Higher learning and memory:
  
  • Memory can be divided in 2 types – Non-declarative Memory and Declarative Memory
    
  • Non-declarative – learning skills, habits, functions – classical conditioning
    
    • The pathway is not well understood, but it is different than the pathways for declarative memory.
      
    • You can destroy the hippocampus, and the person will not have any type of memory, but you can give that person piano lessons, and they will be able to play the piano but not remember having taken lessons.
      
    • (ex. Taxi – Christopher Lloyd as Jim Ingatowski – Elane worked at art gallery - invited Jim….piano player never showed…Jim played…burned brain out by drugs – "Damn I must have taken lessons") – this could possibly happen if you had destruction of your Hippocampus
      
  • Declarative – (is what you think of as memory) people, places, events, facts of science, what happened, what events just occurred. These memories must pass through the Hippocampus before being recorded in the Cerebral Cortex.  A memory is recorded in a specific area (if you smelled something it is stored in the olfactory cortex, or if you saw something it is stored in the visual cortex, but it has to pass through the Hippocampus.  Declarative memory has 3 parts: (these names vary by year)
    
    • 1.) Immediate Buffer – this is what you are currently using. It is a constant firing circuit or groups of circuits.  Information is entered by adjusting the firing rate of the circuits.  You lose stuff all the time out of the immediate buffer. 
      
    • 2.) Short-term memory – is going to last for a few hours.  What happens is a synapse is firing briefly at a high frequency, and the receiving neuron will become more sensitive to that firing. The receiving neurons temporarily experience a greater voltage swing in response to the firing.  It is a local response and it does not involve the nucleus. The changes to the synapse (synaptic plasticity) will last hours.
      
    • 3.) Long-term memory – memory enters in a short term memory, but instead of only being stimulated once, a few minutes later a second burst will occur, and then a third burst will occur – these are called Temporal Firing Patterns (patterns of rapid firing bursts as they are coming in).  These repeated bursts stimulate action potentials to open Calcium channels, and Calcium influxes into the target neuron. The Calcium ions will activate Protein Kinases.  The temporal firings, temporal firing patterns, and the timing of the bursts set up a chemically responsive pathway to the nucleus. Variations in these temporal patterns and timings set up different pathways, but if we are trying to set up long term memory the Calcium ions will activate a Protein Kinase that activates a cyclic AMP response element binding protein called CREB. CREB will go into the nucleus to activate genes and produce synaptic strengthening proteins. The synaptic changes are permanent and we have long term memory.  This is no the only thing that the neuron can do, a lot of things can occur by changing the temporal firing patterns. How the Calcium influxes makes a difference too. Some of the stuff comes in and makes a permanent memory, but some of the stuff (that you didn't want to remember or stuff that you are not aware of) associated with that also might be committed to memory.
      
    • This neuron can be taught to different things by changing the temporal firing patterns.
      
  • Our memories are NOT that good – it is so easy to put false memories into someone's head.
    
    • Imprinting false memories is very easy to do.
      
    • Generally traumatic memories are the ones that last.
      
      • Ex. Where were you last week vs. Where were you on 9/11.
        
      • If we have a beer party and we videotaped it.  Group A met up 6 months later, and so did Group B (to recall what happened at the party).  But Group B had a Shill (someone who wasn't at the party) in their group placing a false memory.  At the 6 month mark the Group B did not agree with the Shill who said that he threw up.  But if Group B comes back in a year, ½ of the group will remember that the Shill threw up at the party.
        

 
 

Blood Cells:

• Blood production is called Hematopoiesis
  
• You didn't start to make blood originally, b/c you were in utero at around the 3^rd week.
  
• We will cover where blood production begins (at the organ), when it wanes (when it goes away from that location)
  
• When in vivo (in utero), and you first started to produce blood – it was produced in the Yolk sac and that began at about the 3^rd week of gestation and waned from the Yolk sac at about the 3^rd month.
  
• Blood is then produced by the Vasculature (blood vessels) – this begins in about the 2^nd month and wanes at about the 5^th month, not exactly sure when it ends.
  
  • The cells creating blood in the vasculature have migrated from the Yolk sac.
    
• When we talk about a new place producing blood, indication that another true migration has begun.
  
• The Liver starts to produce blood late in the 2^nd month and wanes at about the 7^th or 8^th month. The liver is the main producer of fetal blood in the middle trimester of gestation.
  
• The Spleen starts to produce blood in the 3^rd month and wanes in 7^th month.
  
• The Bone marrow starts to produce blood in the 4^th month and ends Post-mortim (it is still going on now).
  
• When we are first making this blood we are only making Red Blood Cells (RBC's), until about the 4^th month the RBC's are larger, about 10um in diameter, are nucleated, and contain a different type of hemoglobin, from the 4^th month on they are replaced with adult type RBC's, little sacs of 8.6um in diameter hemoglobin.
  
• At about 3 months of gestation, Platelet production will occur (deals with blood coagulation).
  
• At about 5 months of gestation, Leukocytes (White Blood Cells) begin to be produced, but an immune response does not occur – they are not functional.
  
  • The Immune system does not start functioning (carrying out an immune response) until 60 days after you are born (ex. true for humans and horses).
    
    • For a Foal, the antibodies do not cross the placenta so that Foal does not have an immune system for 60 days.  It is very important for the Foal to get milk in order to get antibodies from the mother. 
      
    • In humans, the IGG (immunoglobin) will cross the placenta, and the baby will get antibodies from the mother when it is born, and the immune response will be from those antibodies to fight things until 60 days pass and it can do an immune response itself.
      
• Red Bone Marrow – when you were born virtually every bone in your body was Red Bone Marrow and it was making blood, but now that you are older blood is only being made in your:
  
  • Proximal Humerous
    
  • Proximal Femur
    
  • Shoulder Girdle (clavicle and scapula)
    
  • Pelvic Girdle
    
  • Axial Skeleton (Rib cage, head, spinal column) – centralized part
    
  • Red Bone Marrow is the largest and most active organs in your body – if we put all of your bone marrow together as a single organ it would rival the size of the liver.
    
  • The lower limbs (ex. shins) and lower arms (ex. hands), are not making any RBC's.
    
  • Since the baby has all of this, they can replace blood almost at the same rate as an adult human (it will replace 5cc's of blood just as fast as an adult).
    
  • Red Bone Marrow is NOT liquid – it is a solid tissue with zones of different types of blood cell production; each zone produces a single type of blood cell, and the zones are held together byAdhesion Molecules.
    
  • All of our blood cells come from a stem cell called a Pluripotent Hemotopoietic Stem Cell (HSC).
    
    • Pluripotent means it can become any cell it wants to become
      
  • The HSC can:
    
    • 1.) Replace itself producing another HSC cell
      
    • 2.) Give rise to Colony Forming Unit cells (CFU-L) (the L stands for Lymphocytes) – the CFU-L is not a lymphocyte but it is destined become one
      
    • 3.) Can produce a cell called CFU-GEMM – this cell can become all the other blood cells that you make