Functional Pre- and Postsynaptic Changes between the Retinohypothalamic Tract and Suprachiasmatic Nucleus during Rat Postnatal Development

Abstract

The suprachiasmatic nucleus (SCN) is the main brain clock in mammals. The SCN synchronizes to the light-dark cycle through the retinohypothalamic tract (RHT). RHT axons release glutamate to activate AMPA-kainate and N-methyl-D-aspartate (NMDA) postsynaptic receptors in ventral SCN neurons. Stimulation of SCN NMDA receptors is necessary for the activation of the signaling cascades that govern the advances and delays of phase. To our knowledge, no research has been performed to analyze the functional synaptic modifications occurring during postnatal development that prepare the circadian system for a proper synchronization to light at adult ages. Here, we studied the pre- and postsynaptic developmental changes between the unmyelinated RHT-SCN connections. Spontaneous NMDA excitatory postsynaptic currents (EPSCs) were greater in amplitude and frequency at postnatal day 34 (P34) than at P8. Similarly, both quantal EPSCs (miniature NMDA and evoked quantal AMPA-kainate) showed a development-dependent increase at analyzed stages, P3-5, P7-9, and P13-18. Moreover, the electrically evoked NMDA and AMPA-kainate components were augmented with age, although the increment was larger for the latter, and the membrane resting potential was more depolarized at early postnatal ages. Finally, the short-term synaptic plasticity was significantly modified during postnatal development as was the estimated number of quanta released and the initial release probability. All of these synaptic modifications in the unmyelinated RHT-SCN synapses suggest that synchronization to light at adult ages requires developmental changes similar to those that occur in myelinated fast communication systems.

Light stimulation during postnatal development is not determinant for glutamatergic neurotransmission from the retinohypothalamic tract to the suprachiasmatic nucleus in rats

“…Jerusalem, Israel). To evoke EPSCs at a level of quantal events by desynchronization of neurotransmitter released by the optic quiasm stimulation, the 2 mM Ca 2+ of the extracellular recording solution (ACSF) was replaced by 3 mM Sr 2+ (Chen & Regehr, 2000; Reyes‐Mendez et al., 2020).…”

“…The EPSC amplitude was estimated from the average of 20 responses elicited at each holding potential. The NMDA EPSC amplitude (at +40 mV) was determined when AMPA–kainate EPSCs (at −60 mV) decayed at 95% (Reyes‐Mendez et al., 2020).…”

“…The overall initial release probability was computed by dividing the cumulative amplitude of the first pulse (that resulted of all neurons belonging to a specific age group) by the cumulative amplitude of the last pulse (15th stimulus), as previously described (Reyes‐Mendez et al., 2020; Taschenberger & von Gersdorff, 2000).…”

“…RHT fibers innervate the rat SCN around P1, experience pruning between P6 and P10, and acquire an adult appearance close to P10 (McNeill et al., 2011; Speh & Moore, 1993). In addition, we have described that during rat postnatal development, the RHT‐SCN synapses display functional changes close to P7, involving modifications at the presynaptic level, such as reduction of short‐term depression (STD), augmentation of the synaptic quantum, and increase in release sites (Reyes‐Mendez et al., 2020). At the postsynaptic level, there is limited information about the development of glutamatergic receptors, NMDA and non‐NMDA, in the SCN.…”

“…During development, the NR2B subunit is constitutively expressed in the ventral SCN, from early (P4) to older postnatal ages (P34), whereas the NR2C and NR2D subunits rise from P8 to P34 (Herrera‐Zamora et al., 2019). Furthermore, the electrically evoked NMDA and AMPA–kainate components increase with age, although the rise was larger for the latter during the development of the SCN (Reyes‐Méndez et al., 2020).…”