Kuhlmann Naila, Wagner Valladolid Miriam, Quesada-Ramírez Lucía, Farrer Matthew J, Milnerwood Austen J
Centre for Applied Neurogenetics (CAN), University of British Columbia, Vancouver, BC, Canada.
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Front Cell Neurosci. 2021 Feb 18;15:569031. doi: 10.3389/fncel.2021.569031. eCollection 2021.
In contrast to the prenatal topographic development of sensory cortices, striatal circuit organization is slow and requires the functional maturation of cortical and thalamic excitatory inputs throughout the first postnatal month. While mechanisms regulating synapse development and plasticity are quite well described at excitatory synapses of glutamatergic neurons in the neocortex, comparatively little is known of how this translates to glutamate synapses onto GABAergic neurons in the striatum. Here we investigate excitatory striatal synapse plasticity in an system, where glutamate can be studied in isolation from dopamine and other neuromodulators. We examined pre-and post-synaptic structural and functional plasticity in GABAergic striatal spiny projection neurons (SPNs), co-cultured with glutamatergic cortical neurons. After synapse formation, medium-term (24 h) TTX silencing increased the density of filopodia, and modestly decreased dendritic spine density, when assayed at 21 days (DIV). Spine reductions appeared to require residual spontaneous activation of ionotropic glutamate receptors. Conversely, chronic (14 days) TTX silencing markedly reduced spine density without any observed increase in filopodia density. Time-dependent, biphasic changes to the presynaptic marker Synapsin-1 were also observed, independent of residual spontaneous activity. Acute silencing (3 h) did not affect presynaptic markers or postsynaptic structures. To induce rapid, activity-dependent plasticity in striatal neurons, a chemical NMDA receptor-dependent "long-term potentiation (LTP)" paradigm was employed. Within 30 min, this increased spine and GluA1 cluster densities, and the percentage of spines containing GluA1 clusters, without altering the presynaptic signal. The results demonstrate that the growth and pruning of dendritic protrusions is an active process, requiring glutamate receptor activity in striatal projection neurons. Furthermore, NMDA receptor activation is sufficient to drive glutamatergic structural plasticity in SPNs, in the absence of dopamine or other neuromodulators.
与感觉皮层的产前拓扑发育不同，纹状体回路组织发育缓慢，在出生后的第一个月内需要皮质和丘脑兴奋性输入的功能成熟。虽然在新皮质谷氨酸能神经元的兴奋性突触中，调节突触发育和可塑性的机制已得到很好的描述，但对于这如何转化为纹状体中GABA能神经元上的谷氨酸突触，人们所知相对较少。在这里，我们在一个可以将谷氨酸与多巴胺和其他神经调质分开研究的系统中，研究兴奋性纹状体突触可塑性。我们检查了与谷氨酸能皮质神经元共培养的GABA能纹状体棘状投射神经元（SPN）的突触前和突触后结构及功能可塑性。在突触形成后，在21天（DIV）进行检测时，中期（24小时）TTX沉默增加了丝状伪足的密度，并适度降低了树突棘密度。树突棘减少似乎需要离子型谷氨酸受体的残余自发激活。相反，慢性（14天）TTX沉默显著降低了树突棘密度，而未观察到丝状伪足密度增加。还观察到突触前标志物突触素-1随时间的双相变化，与残余自发活动无关。急性沉默（3小时）不影响突触前标志物或突触后结构。为了在纹状体神经元中诱导快速的、活动依赖的可塑性，采用了一种化学NMDA受体依赖的“长时程增强（LTP）”范式。在30分钟内，这增加了树突棘和GluA1簇的密度，以及含有GluA1簇的树突棘的百分比，而不改变突触前信号。结果表明，树突突起的生长和修剪是一个活跃的过程，需要纹状体投射神经元中的谷氨酸受体活性。此外，在没有多巴胺或其他神经调质的情况下，NMDA受体激活足以驱动SPN中的谷氨酸能结构可塑性。
