Converging integration between ascending proprioceptive inputs and the corticospinal tract motor circuit underlying skilled movement control

Abstract

Converging interactions between ascending proprioceptive afferents and descending corticospinal tract projections are critical in the modulation and coordination of skilled motor behaviors. Fundamental to these processes are the functional inputs and the mechanisms of integration in the brain and spinal cord between proprioceptive and corticospinal tract information. In this review, we first highlight key connections between corticospinal tract motor circuit and spinal interneurons that receive proprioceptive inputs. We will also address corticospinal tract access to the presynaptic inhibitory system in the spinal cord and its role in modulating proprioceptive stimuli. Lastly, we will focus on the corticospinal neuron influences on the dorsal column nuclei complex, an integration hub for processing ascending somatosensory information.

Keywords: corticospinal neurons; motor cortex; proprioceptive sensory neurons; spinal cord.

Figure 1.

Spinal integration of the proprioceptive sensory-motor circuit and the sensorimotor corticospinal tract system. Connectivity of spinal circuitry between convergent corticospinal tract (CST) axons (red) and proprioceptive inputs (blue) onto spinal interneurons (gray) (A–E). Rodents form rare direct monosynaptic connections between CST axons (dotted red) and motoneurons (purple). (A) Connectivity of motor CST axons (red) onto propriospinal Chx10 (V2a) interneurons (gray) in cervical spinal cord levels 3 and 4 (C3–C4) [7**]. Propriospinal V2a interneurons relay information to the lateral reticulate nucleus (LRN) and cerebellum and are critical for skilled reaching [23]. (B) Connectivity of CST axons (red) from sensorimotor cortex to spinal Isl1 and Atoh interneurons (gray) [7**]. Atoh interneurons target the cerebellum and thalamus and are involved in coordination of the hindlimb [25]. dI3 interneurons are critical for integrating for integrating sensory feedback for paw grip [26]. (C) Connectivity of CST inputs (red) onto Tcfap2β and Sat1/2 premotor neurons (gray) located in laminae IV and V [24*]. These premotor neurons may encode for motoneuron activation for motor synergy programs [24*]. (D) Connectivity of CST inputs (red) onto dorsal spinocerebellar (dSC) neurons, known as Clarkes column dSC neurons (gray) [28*]. dSC neurons receive direct excitatory or indirect inhibitory (D’; see inset) inputs via inhibitory interneurons (e.g. GABA and glycine) [28*]. dSC relay proprioceptive information to the cerebellum for peripherally derived sensory feedback [28*]. (E) Connectivity of CST inputs (red) [31, 32] and proprioceptive afferents (blue) [33] onto Renshaw cells (gray) a class of spinal inhibitory interneurons that receive recurrent collaterals from alpha motoneurons (purple) [30]. Renshaw cells project back to alpha motoneurons and provide inhibitory feedback (i.e. GABA, glycine) and is called recurrent inhibition [30]. (F) Connectivity of CST inputs (red) onto last-order GABApre inhibitory interneurons (gray) which modulate the proprioceptive sensory-motor reflex circuit and produce primary afferent depolarization (PAD) [7**, 37, 38*]. (F’; see inset) Last order GABApre interneurons form axo-axonic synapses onto proprioceptive afferent terminals, expressing the GABA synthesizing enzyme GAD2 (also known as GAD65) [38*, 42]. GABApost interneurons which synapse directly on motoneurons, express GAD1 (also known as GAD67) [38*, 42]. (F) CST axons (red) can also depress PAD, by activating inhibitory interneurons (black), which in turn, inactivate first-order PAD interneurons (light gray), enhancing Ia afferents [46, 47]. dSC – dorsal spinocerebellar; LRN – lateral reticular nucleus; MN – motoneuron; IN – interneuron; PN – propriospinal; CST – corticospinal tract; P – proprioceptive neuron; GAD65/67 – glutamic acid decarboxylase; vGlut1 – vesicular glutamate transporter; GABA – gamma-aminobutryric acid.

Figure 2.

The dorsal column nuclei complex: an integration center for processing ascending proprioceptive information and descending sensorimotor corticospinal inputs. (A) Schematic diagram showing corticospinal (CS) neurons (red) originating in M1 (area 4) and area 3a sending axon collaterals towards proprioceptive regions (rostral and ventral portion) of the dorsal column nuclei complex (DCN) (blue) as well as cervical spinal cord (see Figure 1) [–59]. Furthermore, purple arrows shows proprioceptive inputs to the DCN complex (blue) and proprioceptive outputs to the cerebellum, inferior olive and ventral posterior lateral (VPL) nucleus of the thalamus. (B) CS inputs (red) make both direct excitatory (i.e. glutamatergic) and/or indirect post inhibitory effects through inhibitory INs (i.e. GABA & glycine) (black) on DCN cells (blue) within the DCN complex [, , –63]. CST inputs enhance relevant proprioceptive stimuli through excitatory interneurons and inhibit non-relevant proprioceptive stimuli via inhibitory interneurons [64*]. Furthermore, ascending proprioceptive information (dark blue) processed in the DCN, are relayed to thalamus (green), and modulated by cortical feedback from proprioceptive cortex (area 3a) and M1 (area 4). VPL – ventral posterior lateral nucleus of the thalamus; X - nucleus X; Z – nucleus Z; ECu – External cuneate nuclei; DCN – dorsal column nuclei; M1 – primary motor cortex