spinal cord circuits Neuroanatomy and Development of the Motor System 2024.pptx

Spinal Circuits: The Neuroanatomy and Development of the Sensorimotor System [email protected]  Decussati on CPG Central pattern generators The Motor System is Hierarchical Development and Evolution progress from one level of h...

Spinal Circuits: The Neuroanatomy and Development of the Sensorimotor System [email protected]  Decussati on CPG Central pattern generators The Motor System is Hierarchical Development and Evolution progress from one level of hierarchy to another Swimming fish Locomotion Precision grip Central pattern Central Pattern Generator Sensory feedback generator Sensory feedback Descending input Descending input Sensory feedback Descending input (especially corticospinal)  Axon projection CPG interneurons Type in embryonic cord V0 Commissural Rostrally Inhibitory (Renshaw cells Rostrally and V1 and Ia ipsilaterally interneurons) Glutamatergic Ipsilaterally and V2 V2a and caudally Inhibitory V2b Excitatory V3 Caudally Commissural Stifani (2014) Frontiers in Cellular Neuroscience doi: 10.3389/fncel.2014.00293  MNs: specified by PAX6, OLIG2, NKX6.1, IN (V1): specified by PAX6, IRX3, DBX2, NKX6.2 Stifani (2014) Frontiers in Cellular Neuroscience doi: 10.3389/fncel.2014.00293 Early in Development Before sensory reflex arcs are complete Motoneurons and central pattern generator neurons are active Activity spreads via gap junctions and synapses Alternation between limbs R = rhythm- generating neurons Excite motoneurones on the same side of the spinal cord directly Ole Kiehn (2016) Nature Rev Neurosci 17(4): 224–23 8. Alternation between flexor Isolated spinal cord in vitro and extensor motoneurons On the same side of the spinal cord Genetically ablated inhibitory interneurons Fully functioning circuit 1a sensory DRG neuron innervating Two types of interneuron from the V1 muscle spindle family proprioceptive RC= Renshaw cells – Recurrent inhibition, neurotransmitter Glycine or Glycine/GABA 1a inhibitory interneurons- receive excitatory input from flexor muscle via 1a fibres from muscle spindles but inhibit extensor motoneurons (or vica versa) also inhibited by Renshaw cells. Neurotransmitter Glycine or Glycine/GABA Can you see how this arrangement generates alternating activity in flexors and extensors? Types of sensory fibres entering CNS via spinal cord Classification Role Conduction Synaptic velocity Targets A Alpha Type 1a fibres from muscle Very Fast Alpha spindle motoneurons Monitor velocity of muscle Large, heavily 1A interneurons stretch myelinated Clarke’s column Cuneate and gracile nuclei Type 1b from Golgi organ in Very Fast Spinal cord tendon interneurons Monitor force of contraction Large, heavily Cuneate and myelinated gracile nuclei A Beta and Type 2 fibres from muscle spindle Fast Spinal cord A Delta Monitor length of muscle and interneurons position in space Quite large and Cuneate and quite heavily gracile nuclei myelinated A gamma Touch, pain, heat, vibration Moderate Spinal cord interneurons Medium sized, Spinothalamic lightly neurons myelinated Cuneate and gracile nuclei C fibres pain, heat Slow Spinal cord interneurons (dorsal horn) Spinothalamic neurons  Sensory feedback from muscles Côté M-P, Murray LM and Knikou M (2018) Front. Physiol. 9:784. doi: 10.3389/fphys.2018.00784 Flexor reflex: multisynaptic pathway Flexor and Crossed Extensor Reflex Neurons activated by the sensory input may also be part of a CPG circuit Long propriospinal Long propriospinal interneurons (PINs) interneurons reciprocally connect the cervical and lumbar spinal cord and contribute to locomotor movement (rodents). (A) Descending PINs form a complex bilateral system with excitatory and inhibitory components to mediate interlimb coordination and to relay information to CPG. most originate from laminae VII-VIII and the deep dorsal horn. They project to non-motoneuronal elements in similar proportion to the ipsilateral and contralateral rostral lumbar cord through the ventrolateral funiculus (red). The ipsilateral population terminals are evenly distributed throughout the gray matter, whereas the projections of the contralateral population are concentrated in laminae VII-VIII. The vast majority of descending PINs are excitatory both on the ipsilateral or contralateral side but the small inhibitory population terminates ipsilaterally. (B)Ascending PINs form a powerful ipsilateral excitatory pathway from the rostral lumbar cord to motoneurons controlling proximal forelimb muscles. Ascending PINs originate mostly from the Côté M-P, Murray LM and Knikou M (2018). Front. Physiol. 9:784. doi: intermediate gray in lumbar spinal cord and 10.3389/fphys.2018.00784 preferentially project ipsilaterally. They project to Transcortical (slow) reflex pathways Clarke’s column (thor and lumb): Prominent group of large cells that receive inputs from Ia afferents, send axons through DSCT to cerebellum Hierarchy not established. Stepping driven by sensory feedback and CPGs in the spinal cord. This disappears then re-emerges as corticospinal influence is established. Corticalisation of movement control. Pathways into spinal cord and basic function Lateral corticospinal tract Voluntary control of distal musculature Anterior corticospinal tract Voluntary control of proximal musculature Reticulospinal tracts (pontine and medullary) Regulate flexor reflexes and initiate patterned activity e.g. locomotion, swallowing Rubrospinal tract Motor control; excitation of flexor muscles Tectospinal tract Mainly cervical termination; orientation to visual stimuli Vestibulospinal tracts Lateral controls antigravity muscles – balance; medial regulates head movements Motor and Sensory pathways in the spinal cord white matter  Locati Tract Origin Function Descending pathways for motor on control Lateral Dorsolateral Cerebral Voluntary motor control including In primates only, corticospinal axons CST cortex fine control of Lateral tracts: Dorsolateral CST synapses directly onto motoneurons, extremities Rubrospinal (contralateral) especially those involved in controlling fine movements Rubrospinal Midbrain Voluntary motor Medial tracts: Vestibulo control (red (contralateral) nucleus) Medial Anterior Cerebral Voluntary motor control (trunk (ventral) cortex muscles) CST Vestibulospi Brainstem Posture and balance nal Tectospinal Midbrain Maintaining head position Reticulospin Brainstem Organising motor output in response al to sensory stimuli. Coarse control of movement. Following Stroke damage to Motor Cortex, initially, severe loss of Voluntary Movement unilaterally (on one side) why? Regain of function over time Enhanced activity in surviving corticospinal fibres (including ipsilateral)? Enhanced activity of other descending pathways e.g Reticulospinal Projects bilaterally (to both sides of spinal cord) so reticulospinal neurons receiving inputs from the undamaged cerebral hemisphere can activate spinal cord neurons on both sides of the spinal cord Monkey Organisation of Descending Pathways Cerebral Cortex projects directly to spinal cord Also projects to midbrain and brainstem centres, e.g corticoreticular projections Lateral Medial  Medulla Neuromodulatory inputs Spinal cord Locus Dorsal Coeruleus horn Noradrenaline Pain inhibition Ventral horn Motor Ventral Raphe output Nuclei Excitatory Serotonin Multiple receptor types that can have inhibitory or excitatory effects Agonists can elicit CPG activity in spinal cord injury victims  Human 10-14 PCW Sensorimotor Rodent E17-19 cortex Corticothalamic and spinal cord circuits developing independently Thalam us ? Dorsal column nuclei Spinal Cord Muscle  Human third trimester, neonatal rodent Sensorimotor Sensorimotor cortex cortex Thalam Once descending us input arrives, there is refinement of spinal cord Dorsal column circuitry. nuclei Spinal Cord Muscle  Reading List As well as any good neuroscience textbook, take a look at Lemon RN (2008) Descending pathways in motor control. Annu Rev Neurosci. 2008;31:195-218. doi: 10.1146/annurev.neuro.31.060407.125547. Review. PMID: 18558853 Zaaimi B et al (2012) Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey. Brain.; 135(7): 2277–2289. doi: 10.1093/brain/aws115. Kiehn O (2016) Decoding the organization of spinal circuits that control locomotion. Nature Rev Neurosci. 17(4): 224–238. Clowry GJ (2007) The dependence of spinal cord development on corticospinal input and its significance in understanding and treating spastic cerebral palsy. Neuroscience and Biobehavioral Reviews 31, 1114-1124. Côté M-P, Murray LM and Knikou M (2018) Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions. Front. Physiol. 9:784. doi: 10.3389/fphys.2018.00784 Dubuc R, Cabelguen J-M, Ryczko D (2023) Locomotor pattern generation and descending control: a historical perspective. J Neurophysiol 130: 401-416 https://doi.org/10.1152/jn.00204.2023