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24b. Discharge Re-considered.docx

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Mac Burnham

Lecture 24 b - Discharge Re-considered I. What are “Brain Waves” and What is Synchrony?  Epileptic discharge is seen as a pathological, hyper-synchronized EEG rhythm.  Hyper-synchronized as well as a hyper-excitable EEG reading Questions : What are “brain waves”? What causes/is synchrony? 1. What are “brain waves” (excluding gamma; faster than 30 hz) Note: Gamma are excluded because traditional EEGs have excluded anything higher than ~30 Hz and typically only recorded from 1-30 Hz because you wanted to avoid the 60 Hz discharge from all the AC current in the walls. Also: the mechanical pens that were used could not follow activity that fast anyway.  Spontaneous patterns of electrical activity, usually recorded with gross electrodes.  Generated by the synchronous activity of thousands of neurons. They are summated slow potentials (occur in the absence of axonal firing – TTX). o This means they are EPSPs and IPSPs that you get in the soma and dendrites. Action potentials are too fast to contribute meaningfully to this. o So the slow potentials seen in the EEG recordings can occur in the absence of axonal firing (action potentials)  Best seen when neurons have a single orientation (cortex in surface EEG recordings, HPC in depth recordings) o Tend to be seen best when you have cells that are lined up.  E.g., dendritic trees are dorsal, cell bodies are in the middle and the axons go out the bottom. This is what we’ve seen in the hippocampus. o So when this lining occurs, you generate very strong fields – these are seen in our EEG recordings.  Can be generated locally. Seen in isolated slices (e.g, HPC). o Chunks of brain taken out are called slices o These EEG patterns can be seen in excised brains (e.g., hippocampal slices) So why would they be locally generated like this?  Possible mechanism: excitatory\inhibitory feedback reverberation – role of local bursting neurons?  Essentially, it would be reverberation in (possibly) resting tissue between excitation, which then triggers inhibition – inhibition is there for a while and it then release, giving you excitation again  Local bursting neurons are neurons which fire in bursts. This is an endogenous characteristic of the neuron. There are a lot of these in CA3 (cornu ammonis 3).  Can be paced by outside structures (thalamus paces cortex in sleep spindles, medial septum paces HPC for theta) o In the cortex, during sleep schedules, we can see that sleep spindles are clearly being paced from the thalamus. There is a tendency for the cortex to fire in a rhythmic way anyway, but it is the thalamus that is giving the spacing for these. o Similar to the cortex/thalamus, the hippocampus is being paced by the mesial septal area. Note: the hippocampus will show some rhythmic waves when it is in vitro (outside the brain), but in certain states, it is definitely the septal area that is pacing hippocampal rhythmic oscillations.  Role of NE? 5 HT? Ach? o With the hippocampus and cortex, we think it is probably distant input of the cholinergic type that is pacing it (could be glutamatergic, we don’t know) o What would the non-specific diffuse projection areas from the brain-stem be doing? There is a hypothesis that they may be supressing this spontaneous oscillation in that when these arousal centers are active, generally, the neocortex is desynchronized.  Are axon potentials produced? Yes for cortical delta; apparently not for other rhythms (except gamma). o It is not clear if they are for alpha, theta or delta  Alpha and theta have modest oscillations – the amplitude is not very high. No AP firing has been demonstrated.  In delta, there are enormously high oscillations. In this case, you seem to conceivably get in the signal cells, a cycle of cell firing with cell silence in between. This is what we see in epilepsy too, but we also see tend to see it in deep sleep (but not as pronounced as epilepsy obviously). Carlson figure. -  HPC theta (rats) – famous example o Theta is not much seen in the human EEG (which is mostly generated from the neocortex). There may be some in the early stages or sleep, perhaps some in dreaming, but it not a typical neocortical pattern. o It is however a very typical hippocampal pattern. It is paced by the thalamus and tends to occur in rats.  HPC theta occurs in HPC when the rat’s Cx (neocortex) is desynchronized (giving you a beta pattern) and the rat is active and exploring, sniffing, etc. When the animal is eating, grooming, etc., the theta disappears So what is the function of EEG patterns?  The function is not really known  Idling of brain? Resting? o One theory was that when nothing important was going on in a patch of brain that it falls back to these rhythmic patterns as a sort of idling structure.  Important function? (theta: processing sensory input? cognitive mapping? learning?) o Others think hippocampal theta is very important. They think it may be when the hippocampus is processing environmental input. Some say it was a cognitively mapping. Essentially all of the hippocampus’s functions are involved with hippocampal theta.  Binding of functionally related areas? o From the sensory input, one path leads to where an object is while another path leads to what it is. If you need to know what it is and where it is at the same time, both centers would be active. The suggestion is (called binding) that when you find two different centers activated at the same time, they’re cooperating on something. Therefore you can look at EEG all over the brain, look for parts of the brain that are synchronized or “bound” together in terms of their EEG rhythms and this shows you brain function. 2. What Causes Synchrony?  Gap junctions? o There are gap junctions between dendrites so that electrical excitation in dendrite could lead to electrical excitation in another.  Electrical fields? o You would be projecting electrical fields to nearby neurons, influencing their firing.  Glia? o These are typically thought of passive and metabolic structures. But more and more people are arguing that they are active partners in neural transmission. It is quite clear that they can give off glutamate in certain instances. o Another feature of glial cells are that they are connected by gap junctions. So excitation in a group of astrocytes could be something that could cause synchrony Figure 9.3 in Chapter 9 :  The excitation during the 1 Hz biphasic wave during slow-wave sleep may have something to do with the fact that seizure threshold is lowest in people who are going to sleep, waking up or asleep o It’s a puzzle because people in delta sleep (SWS) have essentially all their arousal systems inhibited with GABA. But the neocortex itself is not inhibited with GABA. It’s just had its sources of facilitation withdrawn. Although blood flow is lower, its not under actually inhibitory control. o This rhythm in delta sleep which is essentially slowly giving you a pattern of firing, not firing, firing etc. for some reason encourages epileptic activity A paroxysmal depolarizing shift (PDS) is a cellular manifestation of epilepsy. First, there is CA2+ mediated depolarization, which causes voltage gated Na+ to open, resulting in action potentials. This depolarization is followed by a period of hyper-polarization mediated by Ca2+-dependent K+ channels or GABA-activated Cl- influx.  PDS is essentially an EPSP caused by calcium and at the same time, the strong EPSP triggers a lot of sodium-based action potentials on it. o You would get these in interictal spiking o II. What is Epileptic Discharge? Definitions: Hughlings Jackson: 1870  “an occasional, an excessive and a disorderly discharge of nerve tissue.” Burnham: this course  An episode of self-sustained – and self-limiting – hyperexcitation in the central nervous system. Questions: ~1:38 do not understand Question: Does epileptic discharge involve hyperexcitation?  Answer: Yes. “During seizure activity, there is a greater increase in cerebral metabolic rate than under any other circumstance. This is seen in measurements of oxygen consumption and glucose uptake and metabolism. It is also reflected in a marked increase if cerebral blood flow.” Question: What could cause self-sustained hyperexcitation?  We don’t know. But there are a couple of theories:  re-entrant excitation o Excitation goes full circle. Neuron A excites neuron B, which excites neuron C. Neuron C then goes full circles and re-excites neuron A.  reverberant excitation o Bouncing back and forth between excitatory group of neurons and inhibitory neurons (we have already seen this as a possible basis for the EEG rhythm we see in sleep). If abnormal activity is present however, you would bounce back and forth between too much excitation and too much inhibition.  role of inhibition - Ohayon’s work o requirement for inhibition  Need inhibition, but why? o evolution out of discharge  The problem of runaway excitation must have been one of the earliest problems of multicellular animals saw. So you can’t have a system that’s setup to have an excitatory excitation circle – there must be some sort of inhibition that’
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