Lecture 26- Enteric nervous system II Flashcards
What are the basic motility patterns in the GIT?
- Two broad physiological conditions each with own characteristic motor activity
- When have not eaten for 3 – 4 hours have the fasted state or interdigestive motor pattern – Also termed migrating motor complex (MMC)
- During and after a meal have fed state – Mixture of segmenting (mixing) and propulsive contractions
- 2 physiologiacl conditions= if you’ve eaten or not, if not eaten for a while= fasted stated
- humans have very sharp division, when start eating= fed state
- MMC= fasted state= easy to study, motor pattern, if it fails= disease usually related to too much bacteria in the gut
- after feeding= fed state= alternating segmented (localised) and peristaltic contraction
What happens in fed state in vitro (in a dish)?
the presence of food in the gut activates the fed state, this happens almost immediately, indicates that the brain is involved but can produce the fed state event without the CNS just takes a bit longer
-automatic system
What are the layers, neurons and interstitial cells of Cajal in the GIT?
- red= immunoreactive to nitric synthase= interneurons (inhibitory) the nitric oxid is inhibitory (where viagra works, the next step in the pathway cGMP, blocks phosphodiestarase= relaxed blood vessels= erect dick dick
- similar mechanism here but makes it go floppy
- green= in myenteric plexus, imunoreactive to calretinin, another message here, subset of neurons that release ACh, these are excitatory, we don’t know why calceritin in these neurons (Ca2+ binding) these also supply longitudinal muscle, nerve transfer
- in SMP(submucous plexus)= the green neurons, vasoactive intestinal peptide, within gut controls water and elctrolyte secretions, the AP activates the secretions, these neurons are secretory (marker is neuropeptide Y= no clear function)
What are the Interstitial cells of Cajal (ICC) and their function?
- In addition to neural pattern generators have pacemakers intrinsic to muscle layers – ICC
- ICC near myenteric plexus are electrically coupled via gap junctions to each other and to smooth muscle cells
- ICC generate rhythmic membrane potential changes (slow waves) in muscle
- Neural activity has little effect on slow wave frequency, but alters probability of slow waves generating action potentials and hence contractions
- myogenic component of the motor control
- provide underlying muscle activity in the GIT
- in guinea pigs they don’t seem to do much
- so can study the ENS without considering ICC
How was it proven that the neurons are responsible for the movements?
- myogenic component of the motor control
- provide underlying muscle activity in the GIT
- in guinea pigs they don’t seem to do much
- so can study the ENS without considering ICC
What is the basic cicrcuit of the GIT ENS?
-can identify features of these neurons, but need to understand how it interacts, this model corresponds to about a milimeter of the gut (out of 1 meter in the guinea pig)
What are some details about the models?
- Models are representations of the real thing
- Can be very abstracted or highly detailed with most accurate being mathematical models based on physics of underlying mechanisms
- Models are essential to all understanding of complex processes
- ultimately the goal of science is to produce models that are so accurate that they stand for the real thing
- an attempt to systemitize the real thing
- rats and mice also used as models, but eg rats do not have a gallbladder so different (biological models)
- mathematical models= can be abstract in here
- you see a model of what you are looking at that, you see a representation of it
How were the intrinsic sensory neurons and their properties identified? (1)
• 1899–Dogielidentified shapes of enteric neurons, neurons of “second type” have axons going to mucosa and processes supplying other myenteric ganglia, the expected pattern for intrinsic sensory neurons
- stimulate the wall of the intestine and can get a response so showed that there are sensory neurons there
- multiple axons, large smooth cell body, lot of outputs per neuron, exactly what you want in a sensory neuron,
How were the intrinsic sensory neurons and their properties identified? (2)
- 1974, Hirst et al identified myenteric neurons with prominent after- hyperpolarizing potentials (AHPs) following action potentials and apparently without synaptic input.
- Neurons without synaptic input can only be sensory neurons
- The AH neurons are Dogiel type II neurons by shape
- But they do have synaptic input recording intracellularly, really big after depolarising potentials, about 50mV! huge (15 seconds) the mother of all after depolarisation in mammalian systems
- also same shape as dogiel type II neurons
- large smooth cell body and many axons
- synaptic input= not ESPS like, really slow esps! unlike what was predicted
- difference in CNS this doesn’t happen, slow signals not seen in stoma, but not seen
- distinct difference, but unsure
What was the key result regarding these neurons?
•Physiologically meaningful chemical stimuli applied to mucosa evoke bursts of action potentials in myenteric AH/Dogiel type II neurons (Kunze et al 1995, Bertrand et al 1997)
- Responses still see
- short chain fatty acid administered = acteate, get burst of APs in that class of neurons, if pH3 (stomach acids) again stimulates APs
- must be sensory neurons!nif synaptic transmission blocked
What is the scientific debate regarding the role of ENS and ICC?
• Despite previous 3 slides, one influential school of thought holds that AH/Dogiel type II neurons cannot be primary sensory neurons, because they receive synaptic input
– On model of dorsal root ganglion cells
• However, some established primary sensory neurons receive synaptic input
– Some DRG neurons (on their terminals)
– Retinal photoreceptors – Mesencephalic primary afferent neurons of the trigeminal tract
• Key logic point – if neuron responds to sensory stimulus without synaptic transmission it must have a sensory function, in addition to any other functions
- but they get synaptic neurons so shouldn’t be sensory neurons!, some primary sensory neurons receive inputs! some dorsal root ganglia onto terminals
- must have a sensory and interneuron function -also are interneurons
What does this synaptic input do?
- ISN (intrinsic sensory neurons) axons connect to other ISNs and excite them – Recurrent excitatory feedback loop (positive feedback)
- Computational modelling shows that AHPs provide inhibition that keeps this network stable
- Interaction of slow EPSPs and AHPs needed if ISN networks are to encode ongoing sensory information
- ISNs can act as interneurons under some circumstances
- ISN network forms one of the pattern generators that regulates mixing
-sensory neurons connected to one another, recurrent excitatory loop (positive feedback), so they need inhibition to not run out of control
