Alexander Bailin H, Barnes Heather M, Trimmer Emma, Davidson Andrew M, Ogola Benard O, Lindsey Sarah H, Mostany Ricardo
Department of Pharmacology, Tulane University School of Medicine, Tulane University, New Orleans, LA, United States.
Neuroscience Program, Brain Institute, Tulane University, New Orleans, LA, United States.
Front Mol Neurosci. 2018 Mar 16;11:83. doi: 10.3389/fnmol.2018.00083. eCollection 2018.
Periodic oscillations of gonadal hormone levels during the estrous cycle exert effects on the female brain, impacting cognition and behavior. While previous research suggests that changes in hormone levels across the cycle affect dendritic spine dynamics in the hippocampus, little is known about the effects on cortical dendritic spines and previous studies showed contradictory results. In this imaging study, we investigated the impact of the estrous cycle on the density and dynamics of dendritic spines of pyramidal neurons in the primary somatosensory cortex of mice. We also examined if the induction of synaptic plasticity during proestrus, estrus, and metestrus/diestrus had differential effects on the degree of remodeling of synapses in this brain area. We used chronic two-photon excitation (2PE) microscopy during steady-state conditions and after evoking synaptic plasticity by whisker stimulation at the different stages of the cycle. We imaged apical dendritic tufts of layer 5 pyramidal neurons of naturally cycling virgin young female mice. Spine density, turnover rate (TOR), survival fraction, morphology, and volume of mushroom spines remained unaltered across the estrous cycle, and the values of these parameters were comparable with those of young male mice. However, while whisker stimulation of female mice during proestrus and estrus resulted in increases in the TOR of spines (74.2 ± 14.9% and 75.1 ± 12.7% vs. baseline, respectively), sensory-evoked plasticity was significantly lower during metestrus/diestrus (32.3 ± 12.8%). In males, whisker stimulation produced 46.5 ± 20% increase in TOR compared with baseline-not significantly different from female mice at any stage of the cycle. These results indicate that, while steady-state density and dynamics of dendritic spines of layer 5 pyramidal neurons in the primary somatosensory cortex of female mice are constant during the estrous cycle, the susceptibility of these neurons to sensory-evoked structural plasticity may be dependent on the stage of the cycle. Since dendritic spines are more plastic during proestrus and estrus than during metestrus/diestrus, certain stages of the cycle could be more suitable for forms of memory requiring formation and elimination of spines and other stages for forms of memory where retention and/or repurposing of already existing synaptic connections is more pertinent.
发情周期中性腺激素水平的周期性振荡会对雌性大脑产生影响，进而影响认知和行为。虽然先前的研究表明，整个周期内激素水平的变化会影响海马体中的树突棘动态，但对于其对皮质树突棘的影响却知之甚少，并且先前的研究结果相互矛盾。在这项成像研究中，我们调查了发情周期对小鼠初级体感皮层中锥体神经元树突棘密度和动态的影响。我们还研究了在发情前期、发情期和发情后期/间情期诱导突触可塑性是否对该脑区突触重塑程度有不同影响。我们在稳态条件下以及在发情周期的不同阶段通过触须刺激诱发突触可塑性后，使用慢性双光子激发（2PE）显微镜进行观察。我们对自然发情的未交配年轻雌性小鼠第5层锥体神经元的顶端树突簇进行成像。在整个发情周期中，树突棘密度、周转率（TOR）、存活分数、形态以及蘑菇状树突棘的体积均保持不变，并且这些参数的值与年轻雄性小鼠相当。然而，虽然在发情前期和发情期对雌性小鼠进行触须刺激会导致树突棘的TOR增加（分别为74.2±14.9%和75.1±12.7%相对于基线），但在发情后期/间情期感觉诱发的可塑性显著降低（32.3±12.8%）。在雄性小鼠中，触须刺激使TOR相较于基线增加了46.5±20%，在发情周期的任何阶段与雌性小鼠相比均无显著差异。这些结果表明，虽然雌性小鼠初级体感皮层中第5层锥体神经元树突棘的稳态密度和动态在发情周期中保持恒定，但这些神经元对感觉诱发的结构可塑性的敏感性可能取决于发情周期的阶段。由于树突棘在发情前期和发情期比发情后期/间情期更具可塑性，发情周期的某些阶段可能更适合需要形成和消除树突棘的记忆形式，而其他阶段则更适合已经存在的突触连接的保留和/或重新利用更为相关的记忆形式。
