IBRO 2023. 11th Word Congress of Neuroscience, 9-13 september 2023, Granada, Spain, Esta publicación es parte del proyecto de I+D+i PID2021-126330OB-I00, financiado por MICIU/AEI/10.13039/501100011033/ y por “FEDER Una manera de hacer Europa”, The spinal dorsal horn receives and integrates a wide variety of somatosensory inputs and is particularly relevant for nociceptive information. This area receives signals directly from the periphery via primary afferents, but also descending inputs from higher centres that modulate the incoming information and the processing by intraspinal circuits (1). Serotoninergic and adrenergic descending systems are two modulatory systems that can have both facilitatory and inhibitory effects on dorsal horn neurons (DHNs) and nociceptive processing (2). The presence of spontaneous activity in spinal circuits has been reported under in vivo and in vitro conditions and may play a fundamental role in the processing of nociceptive information by modulating the excitability of the spinal circuits. Our aim was to investigate the modulatory role of the adrenergic and serotonergic descending systems on the spontaneous activity of DHNs, the occurrence of coordinated activity in spinal circuits and the generation of dorsal root potentials in primary afferents., Agencia Estatal de Investigación

Neuroscience 2024, 05/10/2024-09/10/2024, Chicago, Estados Unidos., Primary afferents are responsible for transmitting the sensory information generated at peripheral receptors to the spinal cord. However, before this information reaches second-order neurons, it can be modulated by presynaptic contacts from dorsal horn neurons. These presynaptic contacts can regulate neurotransmitter release by modifying the excitability of synaptic terminals and thus the efficiency of information transmission. Using opto- and chemogenetic techniques, we wanted to investigate how changes in the excitability of primary afferent terminals can modify spontaneous activity in spinal cord circuits. These studies were carried out using in vitro spinal cord preparations from neonatal mice expressing channelrhodopsin-2 (ChR2), Archaerhodopsin-3 (ArchT) and hM4Di-DREADD in primary afferent neurons under the control of the advillin promoter. Glass suction electrodes were used to record dorsal root activity, while multi-electrode arrays were used to record the activity of neurons in the dorsal horn. An adjacent dorsal root was electrically stimulated to activate primary afferents and generate synaptic responses in both the recording root and dorsal horn neurons. ChR2 activation by light at 455nm caused a depolarization in the afferents contained within the root, together with abolition of spontaneous dorsal root potentials (sDRPs). There was also an increase in the spontaneous firing of most dorsal horn neurons, but this enhancement was accompanied by a loss of coordination between neurons. Activation of hM4Di-DREADD with clozapine N-oxide led to a reduction in sDRP and in the firing frequency of dorsal horn neurons, with a concomitant loss of coordinated activity. On the other hand, ArchT stimulation with light at 567nm hyperpolarized the afferents in the dorsal root and increased sDRP amplitude. The activity of dorsal horn neurons showed a moderate increase during afferent hyperpolarization with an enhancement of coordinated activity. The responses produced by the electrical stimulation of an adjacent dorsal root were inhibited by both depolarization and hM4Di-DREADD activation, but were unchanged during the hyperpolarization induced by ArchT. These results show that the ability of primary afferents to transmit information can be strongly regulated by acting at their central terminals inside the cord. Primary afferents terminals work as an essential component in maintaining coordination in the spontaneous activity of spinal circuits, contributing to adjust their excitability., Agencia Estatal de Investigación

IBRO 2023. 11th Word Congress of Neuroscience, 9-13 september 2023, Granada, Spain, Esta publicación es parte del proyecto de I+D+i PID2021-126330OB-I00, financiado por MICIU/AEI/10.13039/501100011033/ y por “FEDER Una manera de hacer Europa”., The excitability of the central terminals of primary afferents (PA) is critical in regulating neurotransmitter release to second-order neurons
located in the spinal cord. Primary afferent depolarisation (PAD) is an important mechanism of presynaptic inhibition that regulates
somatosensory inputs to the spinal cord, and primary afferent
hyperpolarisation (PAH) can produce opposite effects (1,2). In
addition, activity in primary afferents may serve as a mechanism for
spreading excitation to spinal cord neurons, thereby maintaining the
excitability of spinal cord circuits (3,4).
Our aim was to investigate how changes in the excitability at PA
terminals modify activity in spinal circuits. By expressing opto- and
chemogenetic tools under the control of the advillin promoter, the
excitability of central terminals of PA was manipulated to test the
influence of these manoeuvres on the rhythmic spontaneous and
induced activity recorded from dorsal roots and dorsal horn neurons., Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación