Straub Flashcards
Describe a reflex with example
Example: Knee jerk reflex General features: involuntary, unconscious triggered by specific stimulus stereotypic fixed response polysynaptic reflex monosynaptic reflex
Give an example of specific stimuli and complex behaviour
Example: Egg retrieval in geese and gulls
Describe other fixed action patterns (FABs) eg.
- many courtship behaviours
- gaping and pecking responses in young birds
Describe FABs
- study of FAPs is particularly linked to work by von Holst, Lorenz and Tinbergen,which can be considered founders of field of neuroethology
- study is based on observation of animal behaviour
- FAPs are innate and species typical
- FAPs are triggered by sign stimulus/releaser – a stimulus that triggers FAP once triggered FAPs are carried out to completion
- today, the term ‘FAP’ has been widely replaced by the term ‘behavioural act’ or ‘behavioural pattern’
Who discovered universal FAPs in humans and what were they?
Eibl-Eibesfeldt observed many different cultures – found evidence for universal FAPs in humans:
- ‘eyebrow flash’ – universal greeting
- emotions in deaf-blind children
- coyness behaviour
Describe the two hypothesis for control of FAPs
Hypothesis 1: FAPs are generated by a sequence of reflexes –> Reflex chainAlso known as the peripheral control hypothesis
Hypothesis 2:The central control hypothesis –a central pattern generator generates sequence of motor behaviours
What arguments exist in central vs peripheral control
Egg retrieval: behaviour carries on after stimulus is removed – suggests that behavioural sequence is generated centrally and not by a reflex chain
FAPs like egg retrieval are too complex for study of neuronal network that controls behaviour
Organisation of basic locomotion is less complex, e.g.
- walking: limbs move forward and backwards
- flying: wings move up and down
- general: locomotion involves rhythmic flexion and extension of muscle groups
- -> highly repetitive, good for experimental analysis
Describe the pacemaker model for central pattern generators (CPG)
- intrinsic oscillator / pacemaker
- imposes activity (rhythm) on network
- To achieve two opposing phases of activity, neuron(s) that are active whilst pacemaker is inactive require mechanism that drives their activity, e.g.:
- Post-inhibitory rebound (PIR)
- Spontaneously active
- Receives constant excitation
Describe the network oscillator model for central pattern generators (CPG)
How to build network oscillator?
Suggestion: Two neurons coupled by excitatory synapse
Problem: Positive feedback – circuit is very unstable!
Describe half centre model for central pattern generators (CPG)
- Two neurons coupled by inhibitory synapses – produces stable oscillation (rhythm)
- requires a mechanism that progressively reduces inhibitory effect: ‘fatigue’, adaptation, progressive self-inhibition
- Post-inhibitory rebound (PIR) can sustain oscillation without constant drive
Describe the sea angel Clione limacina
- Wings are modified foot of snail
- swimming consists of two alternating phases:
dorsal flexion (D-phase)
ventral flexion (V-phase) - Clione CNS
few thousand neurons
clustered in a small number of central ganglia
Describe the ID of Clione swimming neurons
- backfilling makes it possible to identify neurons with axons in a specific nerve
place cut end of nerve into dye
dye is taken up by axon and migrates to cell body - mapped neurons can be impaled with intracellular electrodes to record their activity
- ~40 motoneurons in total including 2 large neurons: 1A: innervates dorsal wing side 2A: innervates ventral wing side smaller motoneurons innervate only certain areas of wing
What did experiments tell us about the generation of swim pattern in Clione
- inactivation of individual motoneurons does not affect overall swim rhythm
- in simultaneous recording from two swim motoneurons
hyperpolarisation of D-phase motoneuron (red box) has no effect on V-phase motoneuron - even photoinactivation of all motoneurons does not interrupt basic rhythm
- m motoneurons are not involved in generation of swim rhythm!
Describe swim interneurons
- swim interneurons have no peripheral processes – can not be identified by backfilling
- can only be identified by systematic search using intracellular electrodes – look for neurons that are active in phase with swim motoneurons
- inactivation of swim interneuron by hyperpolarisation (red box) stops swim rhythm
Describe how swim interneurons are involved with pattern generation in Clione
- Clione has two groups of swim interneurons called 7 and 8
swim interneurons 7 are active during D-phase
swim interneurons 8 are active during V-phase - interneurons 7 and 8 are connected by inhibitory synapses
- interneurons in the same group are electrically coupled
- swim interneurons fire on rebound from inhibition ( post-inhibitory rebound)
Describe the Clione CPG as a half centre oscillator with a twist
- Clione swim CPG has all the elements of a half-centre oscillator
- rhythm generation can be fully explained by connections between different interneuron types
- Swim interneurons possess intrinsic bursting property!
- Swim rhythm generation is result of the combination of intrinsic cellular properties and network properties
SUMMARY FAP, MODELS, CLIONE
- Fixed action patterns are innate behaviours triggered by a sign stimulus/releaser
- Fixed action patterns are centrally controlled
- Various models have been proposed for the central control of rhythmic behaviours including:
pacemaker neurons
half-centre oscillators
closed-loop rhythm generators - Swim rhythm in the marine snail Clione is generated by a central pattern generator with all the features of a half-centre oscillator
- In addition, the interneurons of the Clione swim pattern generator also have intrinsic bursting properties so, they have the potential to function as pacemaker neurons
Describe the neuroanatomy of the tadpole
- Hatchling tadpole
Spinal cord: ~100 mm diameter
- Eight types of spinal neurons including: motoneurons: commissural interneurons descending interneurons dorsolateral interneurons dorsolateral commissural interneurons Rohon-Beard neurons
- Spinal neurons form longitudinal columns of 100-300 cells on each side of CNS
Describe tadpole swim motor neuron
- motoneurons show rhythmic activity in response to brief tail stimulus —> swim episode
- activity of left and right motoneurons alternates (like pattern of laying bricks)
Describe tadpole swim CPG
- Three neuron types are sufficient to generate basic swimming pattern
- All three types show similar activity pattern:
fire single AP during fictive swimming
are tonically excited
receive mid-cycle inhibition - Neurons form half-centre oscillator
Describe what was found in Roberts, Soffe, Perrins (1998) in Neurons, Networks, and Motor Behavior (SUMMARY)
- Commissural interneurons project to opposite site where their axon branches and projects both rostrally and caudally
- Commissural interneurons are responsible for mid-cycle inhibition (Glycine)
- Some have also ipsilateral axons, presumably responsible for recurrent on-cycle inhibition of sensory decussating interneurons (dlc), etc.
- Descending interneurons project caudally on the same side of the cord
- Provide fast AMPA excitation to more caudal neurons and slow NMDA excitation that sustains next cycle
- Motoneurons have peripheral axons, but also descending longitudinal axons that make central synapses (ACh)
- PIR plays a role in pattern generation
- Tonic drive is provided by cycle-by-cycle feedback due to slow NMDA excitation
- Other mechanisms might also play a role
Describe the activation of swim CPG
- Rohon-Beard neurons innervate trunk skin
- RB neurons have longidutinal axons in dorsal spinal cord
- Excite dorsolateral (dl) and dorsolateral commissural (dlc) sensory interneurons
- Trigger activity in swim CPG
How does motoneuron activity propagate?
- from head to tail
- During swimming, waves of bending pass from the head to the tail
- Progression can also be seen in motoneuron activity in isolated spinal cord
What are the two hypothesis for how a wave of activity is propagated
Hypothesis 1:
- single oscillator – variable delays:signal takes longer to reach caudal segments than rostral segments
- Unlikely because:
CPG elements are distributed along the whole length of spinal cord
stretches of spinal cord can be isolated and show rhythmic activity —> CPG is distributed along the spinal cord
Hypothesis 2:
- tadpole spinal cord represent a chain of unitary oscillators
- leading oscillator hypothesis:
each CPG generates rhythm
CPG with fastest rhythm sets overall frequency and co-ordinates activity in other CPGs - rostral-caudal wave propagation requires gradient from head to tail that ensures more rostral CPGs oscillate faster than more caudal CPGs
How is activity in unitary oscillators coordinators
- spinal cord shows rostral-caudal gradient of excitability:
rostral motoneurons are more depolarised during swimming than caudal motoneurons
rostral motoneurons also receive larger midcycle inhibition - prediction:changing excitability of caudal segments changes rostral-caudal delay
How is excitability manipulated in caudal segments and what does it change
- glutamate is excitatory neurotransmitter involved in swimming
- NMDA application (glutamate receptor agonist) to caudal segments increases excitability in these segments and shortens or even reverses rostral-caudal delay
- AP5 application (glutamate receptor antagonist) to caudal segments decreases excitability and increases rostral-caudal delay
Describe longitudinal gradients in exon distribution
- highest number of axons originating from dorsolateral commissural interneurons (dlc), dorsolateral ascending interneurons (dca) and descending interneurons (dIN) are found at rostral end of spinal cord
- could be morphological basis for longitudinal gradient in excitability
Describe lamprey swim CPG
- could be morphological basis for longitudinal gradient in excitability
What is the leading oscillator hypothesis in lamprey
- as in tadpole, glutamate is excitatory neurotransmitter involved in swimming
- separating the spinal cord into three pools and applying different concentrations of the glutamate agonist NMDA alters wave propagation:
- same concentration in all pools —> rostral-caudal wave (forward swim)
- high concentration in caudal pool —-> caudal-rostral wave (backward swim)
- high concentration in middle pool —-> two waves propagating rostrally and caudally
SUMMARY: TADPOLE AND LAMPREY
- Swimming in tadpole and lamprey consists of undulatory body movements that progress as a rostral-caudal wave
- Rhythms are generated by CPG with characteristics of a half-centre oscillator
- Spinal cord can be considered as a chain of unitary oscillators/CPGs
- Segment with fastest frequency leads wave, other segments follow with a specific phase lag generation of a propagating wave
Describe kinematic analysis of walking
- Eadweard Muybridge looked at horses running by taking pictures along a track
- step cycle consists of two phases:
stance (support) phase:
~ anterior extreme position —> posterior extreme position
~ limb moves backward relative to body
~ limb is loaded by part of body weight and also develops propulsive force - swing (transfer) phase:
~ posterior extreme position —> anterior extreme position - three joints:
~ hip, knee, ankle
~ perform flexion and extension movements - hip joint: single cycle of flexion and extension per step
- knee and ankle joint: two peaks of flexion and extension per step
How are the two step phases affected by changes in speed
speed changes mainly due to change in duration of stance phase, smaller changes in swing phase
How is locomotor pattern changed with speed
- changes interlimb coordination
- sequence of foot contacts in quadruped animals:
Describe the sequence and phase of walking
- sequence:LHLFRHRF
- all four limbs out of phase
Describe the sequence and phase of trotting
- sequence:LH/RFLF/RH
- diagonal limbs in phase with each other
Describe the sequence and phase of pacing
- sequence:LH/LFRH/RF
- limbs on one body side in phase with each other
Describe the sequence and phase of galloping
- sequence:LH/RHLF/RF
- pair of limbs in phase with each other
Describe neuronal control of walking
- Each limb is controlled by its own controller
~ First proposed by von Holst in 1938
~ Evidence:
Stepping rhythm in different limbs can differ from each other; e.g. animals and humans walking on a treadmill with split belt - Various gaits are controlled by a single neuronal network
Evidence:
~ Temporal characteristics of step cycle change gradually over wide range
~ Basic pattern of joint movements and muscle activity persists at various speeds/gaits
~ Changes in gait patterns can be achieved by changing single parameter the phase relationship between individual limb controllers
Describe location of neuronal network for walking
- transection experiments:
~ transection at level of superior colliculus (SC) just posterior to corpus mammilary CM creates mesencephalic cat:
recovers ability to stand and walk
walking is very machine-like
~ transection at more caudal levels:
no recovery of spontaneous walking
-basic neuronal network for locomotion located in spinal cord, posterior brainstem and cerebellum - Identification of Mesencephalic Locomotor Region (MLR)
Describe walking in mesencephalic cat
- set-up enables recording of cellular activity during walking
- walking in mesencephalic cat can be triggered by electrical stimulation of mesencephalic locomotor region (MLR)
- but, destruction of MLR does not abolish cats ability to walk
Describe 2 experiments to do with function of MLR
Experiment 1:
- MLR stimulated at constant level, speed of treadmill was gradually decreased
- decrease in step cycle frequency, MLR does not control cycle frequency
Experiment 2:
- MLR stimulated at increasing levels, speed of treadmill was kept constant
- increase in forcechange in gait pattern/phase-relationship between legs
Conclusion:
- MLR activity determines intensity of muscle contraction
- MLR activity affects muscle force and limb co-ordination
Describe the role of the spinal cord in walking
- low spinal cats: transection of spinal cord in thoracic region
~ can perform stepping movements when placed on treadmill and body weight is supported - movements are weak and not-well coordinated
- strength and coordination can be improved by application of clonidine (a2-noradrenergic receptor agonist)
- Conclusion
limb controller present in spinal cord
weak movements due to insufficient excitatory drive
Is limb stepping controlled by CPG?
- removal of sensory feedback by:
~ paralysing preparation using muscle relexant
~ deafferentation (cutting dorsal roots that carries sensory inputs)
spinal cord does not rely on sensory feedback to create rhythmic activity
How do we know one rhythm has multiple CPGs
- cooling blocks neuronal activity in affected areas
- cooling of L5 does not affect rhythm activity in L4
- cooling of L5 blocks rhythmic activity in more caudal spinal cord segments
So… CPG exists in L2-L4 - destruction of grey matter in L3/L4
~ rhythm generation in L5 and more caudal segments remains unchanged
~CPG also exists in L5-L7 - destruction of grey matter in L3/L4+ L6/L7 L5 still able to generate rhythm, i.e. contains CPG
Conclusions
- stepping is controlled by local oscillatory networks
- individual oscillators are coordinated into one single rhythm generator
Describe neuronal elements of limb CPG
- Identification by:
Activity-dependent labelling
Genetic approaches
Electrophysiology
Only about 0.1% of spinal cord neurons appear to be part of CPG
Describe models for limb CPG
Unit burst model: - Individual CPGs for each joint - Coupled to generate overall limb movement pattern Two level CPG model: - Rhythm generation - Pattern generation
Describe contribution from endogenous bursters
- Hb9 interneurons possess endogenous bursting properties
- Membrane potential oscillations can be induced by low extracellular calcium and/or a combination of N-methyl-aspartate (NMA), serotonin (5-HT) and dopamine
- Membrane potential oscillations persist in presence of TTX (i.e. do not require APs and synaptic activity)
SUMMARY STEPPING CPG LOCOMOTION
- stepping involves alternate activity in limb extensor and flexor muscles
- speed changes is mainly due to shortening/lengthening of stance phase
- speed changes lead to changes in interlimb coordination (walk, trot, gallop)
- stepping CPG is located in spinal cord, additional elements in lower brain stem (control strength and coordination)
- stepping is controlled by multiple CPGs that are unified in one locomotion controller
- actual stepping CPG has not been identified
