Cognitive & Neural Systems Program, Boston University, Boston, Massachusetts.
J Neurophysiol. 2020 Aug 1;124(2):544-556. doi: 10.1152/jn.00238.2019. Epub 2020 Jul 1.
Significant evidence has accumulated to support the hypothesis that hippocampal region CA1 operates as an associative mismatch detector (e.g., Hasselmo ME, Schnell E, Barkai E. 15: 5249-5262, 1995; Duncan K, Curtis C, Davachi L. 29: 131-139, 2009; Kumaran D, Maguire EA. 27: 8517-8524, 2007; Lisman JE, Grace AA. 46: 703-713, 2005; Lisman JE, Otmakhova NA. 11: 551-568 2001; Lörincz A, Buzsáki G. 911: 83-111, 2000; Meeter M, Murre JMJ, Talamini LM. 14: 722-741, 2004; Schiffer AM, Ahlheim C, Wurm MF, Schubotz RI. 7: e36445, 2012; Vinogradova OS. 11: 578-598 2001). CA1 compares predictive synaptic signals from CA3 with synaptic signals from EC3, which reflect actual sensory inputs. The new CA1 pyramidal model presented here shows that the distal-proximal segregation of synaptic inputs from EC3 versus CA3, along with other biophysical features, enable such pyramids to serve as comparators that switch output encoding from a brief burst, for a match, to prolonged tonic spiking, for a mismatch. By including often-overlooked features of CA1 pyramidal neurons, this new model allows simulation of pharmacological effects that can eliminate either the match (phasic mode) response or the mismatch (tonic mode) response. These simulations reveal that dysfunctions can arise from either too much or too little ACh stimulation of the muscarinic receptors that control KCNQ channels. Additionally, a dysfunction caused by administration of an -methyl-d-aspartate antagonist could be rescued by simultaneous administration of a KCNQ channel agonist, such as retigabine. Hippocampal region CA1 operates as an associative mismatch detector, comparing predictive signals from CA3 with signals from EC3 reflecting sensory inputs. This new CA1 pyramidal model shows that biophysical features enable these comparators to switch output between brief bursts for matches and tonic spiking for mismatches. This suggests that cognitive learning models (e.g., predictive coding) may require much less match/mismatch circuitry than commonly assumed. Additional simulations illuminate deficits seen in psychiatric disorders and drug-induced states.
大量证据支持海马区 CA1 作为关联失配检测器的假说（例如，Hasselmo ME、Schnell E、Barkai E. 15: 5249-5262, 1995；Duncan K、Curtis C、Davachi L. 29: 131-139, 2009；Kumaran D、Maguire EA. 27: 8517-8524, 2007；Lisman JE、Grace AA. 46: 703-713, 2005；Lisman JE、Otmakhova NA. 11: 551-568 2001；Lörincz A、Buzsáki G. 911: 83-111, 2000；Meeter M、Murre JMJ、Talamini LM. 14: 722-741, 2004；Schiffer AM、Ahlheim C、Wurm MF、Schubotz RI. 7: e36445, 2012；Vinogradova OS. 11: 578-598 2001）。CA1 将来自 CA3 的预测性突触信号与来自 EC3 的反映实际感觉输入的突触信号进行比较。这里提出的新 CA1 金字塔模型表明，EC3 与 CA3 的突触输入的远近分离，以及其他生物物理特征，使这些金字塔能够作为比较器，将输出编码从短暂爆发（匹配）切换为持续紧张性放电（失配）。通过包括 CA1 金字塔神经元中经常被忽视的特征，这个新模型允许模拟可以消除匹配（相模式）响应或失配（紧张模式）响应的药理学效应。这些模拟表明，功能障碍可能是由于控制 KCNQ 通道的毒蕈碱受体的 ACh 刺激过多或过少引起的。此外，通过给予 -甲基-d-天冬氨酸拮抗剂引起的功能障碍可以通过同时给予 KCNQ 通道激动剂（例如 retigabine）来挽救。海马区 CA1 作为关联失配检测器，比较 CA3 的预测信号与反映感觉输入的 EC3 的信号。这个新的 CA1 金字塔模型表明，生物物理特征使这些比较器能够在匹配时在短暂爆发和失配时在紧张性放电之间切换输出。这表明认知学习模型（例如，预测编码）可能需要比通常假设的更少的匹配/失配电路。其他模拟阐明了精神疾病和药物诱导状态中观察到的缺陷。
