Neurocomputational and Language Processing Laboratory, Institute of Physics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 91501-970, Brazil.
Neuroscience Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90050-170, Brazil.
Learn Mem. 2020 Nov 16;27(12):493-502. doi: 10.1101/lm.052217.120. Print 2020 Dec.
During the first ten postnatal days (P), infant rodents can learn olfactory preferences for novel odors if they are paired with thermo-tactile stimuli that mimic components of maternal care. After P10, the thermo-tactile pairing becomes ineffective for conditioning. The current explanation for this change in associative learning is the alteration in the norepinephrine (NE) inputs from the locus coeruleus (LC) to the olfactory bulb (OB) and the anterior piriform cortex (aPC). By combining patch-clamp electrophysiology and computational simulations, we showed in a recent work that a transitory high responsiveness of the OB-aPC circuit to the maternal odor is an alternative mechanism that could also explain early olfactory preference learning and its cessation after P10. That result relied solely on the maturational properties of the aPC pyramidal cells. However, the GABAergic system undergoes important changes during the same period. To address the importance of the maturation of the GABAergic system for early olfactory learning, we incorporated data from the GABA inputs, obtained from in vitro patch-clamp experiment in the aPC of rat pups aged P5-P7 reported here, to the model proposed in our previous publication. In the younger than P10 OB-aPC circuit with GABA synaptic input, the number of responsive aPC pyramidal cells to the conditioned maternal odor was amplified in 30% compared to the circuit without GABAergic input. When compared with the circuit with other younger than P10 OB-aPC circuit with adult GABAergic input profile, this amplification was 88%. Together, our results suggest that during the olfactory preference learning in younger than P10, the GABAergic synaptic input presumably acts by depolarizing the aPC pyramidal neurons in such a way that it leads to the amplification of the pyramidal neurons response to the conditioned maternal odor. Furthermore, our results suggest that during this developmental period, the aPC pyramidal cells themselves seem to resolve the apparent lack of GABAergic synaptic inhibition by a strong firing adaptation in response to increased depolarizing inputs.
在出生后的前十天(P),如果新生啮齿动物与模拟母体护理成分的热触觉刺激配对,它们可以学习对新气味的嗅觉偏好。在 P10 之后,热触觉配对对于条件作用变得无效。目前对这种联想学习变化的解释是蓝斑核(LC)到嗅球(OB)和前梨状皮层(aPC)的去甲肾上腺素(NE)输入的改变。通过结合膜片钳电生理学和计算模拟,我们在最近的一项工作中表明,OB-aPC 回路对母体气味的短暂高反应性是另一种机制,也可以解释早期嗅觉偏好学习及其在 P10 后停止。该结果仅依赖于 aPC 锥体神经元的成熟特性。然而,GABA 能系统在此期间经历重要变化。为了解释 GABA 能系统成熟对早期嗅觉学习的重要性,我们将从这里报告的 P5-P7 龄大鼠 aPC 体外膜片钳实验获得的 GABA 输入数据纳入我们之前出版物中提出的模型。在具有 GABA 突触输入的年轻于 P10 的 OB-aPC 回路中,对条件化母体气味有反应的 aPC 锥体神经元的数量增加了 30%,而没有 GABA 能输入的回路则增加了 30%。与具有成年 GABA 能输入特征的其他年轻于 P10 的 OB-aPC 回路相比,这种放大倍数为 88%。总之,我们的结果表明,在年轻于 P10 的嗅觉偏好学习期间,GABA 能突触输入可能通过去极化 aPC 锥体神经元起作用,从而导致锥体神经元对条件化母体气味的反应放大。此外,我们的结果表明,在这个发育阶段,aPC 锥体细胞本身似乎通过对增加的去极化输入的强烈放电适应来解决 GABA 能突触抑制的明显缺乏。