Memory encoding and storage in cortical circuits: electrophysiological studies

记忆痕迹被认为是由同时激活的神经元网络组成的，新的网络可以通过突触连接强度的长期增加（或减少）形成。海马旁皮质区，包括内嗅皮质和嗅周皮质，在记忆编码过程中处理感觉和联想信息。我实验室的研究主要集中在调节性神经递质和激素（乙酰胆碱、5-羟色胺、多巴胺和雌激素）如何调节内嗅皮层内的突触通讯和神经元兴奋性。调节性递质在记忆形成中起着关键作用，因为它们强烈影响感官信息的持续处理和突触强度的长期变化的诱导。在清醒大鼠的实验中，通过记录突触输入的短暂电刺激诱发的突触反应来监测突触连接强度的变化。来自脑切片中单个神经元的记录也用于研究介导突触连接变化的细胞机制。第一个主要的研究方向是研究神经调质在内嗅皮层的突触输入中的作用，以及多个输入通路之间的相互作用。从梨状皮质和嗅周皮质的输入之间的异突触相互作用将被研究，以表征多模态感觉整合的细胞基础。内嗅皮层接收来自丘脑旁核的强输入，我们将确定5-羟色胺如何影响丘脑旁核神经元的突触反应和兴奋性，以及这如何影响内嗅皮层。雌激素促进认知功能，增强内嗅皮层的兴奋性突触传递，我们现在将确定参与的雌激素受体，并检查雌激素对抑制性和胆碱能突触传递的影响。第二个主要的研究方向是特别关注由递质多巴胺引起的内嗅回路的变化，这种变化可能会促进对与动机和奖励相关的刺激的反应。与奖赏相关的条件性线索激活多巴胺神经元，我们将确定这些线索如何影响内嗅神经元的突触反应和细胞放电。我们还将确定多巴胺在控制突触强度持续增加和减少的诱导中的作用。光遗传刺激技术将被用来确定多巴胺的紧张性和阶段性突触释放如何影响兴奋性传递和内嗅神经元的兴奋性。这项研究计划将确定基本的神经元机制，通过这些机制，神经调质调节内嗅皮层的电路，以促进感觉处理和记忆功能。

Memory traces are thought to consist of networks of simultaneously activated neurons, and new networks can be formed through long-lasting increases (or decreases) in the strength of synaptic connections. Parahippocampal cortical regions, including the entorhinal and perirhinal cortex, process sensory and associational information during the encoding of memory. Research in my lab focusses on how modulatory neurotransmitters and hormones (acetylcholine, serotonin, dopamine, and estrogens) can modulate synaptic communication and neuronal excitability within the entorhinal cortex. Modulatory transmitters play a critical role in memory formation because they powerfully affect both the ongoing processing of sensory information, and the induction of long-lasting changes in synaptic strength. In experiments in the awake rat, changes in the strength of synaptic connections are monitored by recording synaptic responses that are evoked by brief electrical stimulation of synaptic inputs. Recordings from individual neurons in brain-slices are also used to investigate the cellular mechanisms that mediate changes in synaptic connections. The first major line of research investigates effects of neuromodulators on synaptic inputs to the entorhinal cortex, and interactions between multiple input pathways. Heterosynaptic interactions between inputs from the piriform and perirhinal cortex will be investigated to characterize the cellular basis of multi-modal sensory integration. The entorhinal cortex receives strong input from the parasubiculum, and we will determine how serotonin affects synaptic responses and excitability in parasubicular neurons, and how this impacts the entorhinal cortex. Estrogens promote cognitive function and enhance excitatory synaptic transmission in the entorhinal cortex, and we will now determine the estrogen receptors involved, and examine effects of estrogen on inhibitory and cholinergic synaptic transmission. The second major line of research focusses specifically on changes in entorhinal circuitry induced by the transmitter dopamine which may promote responses to stimuli associated with motivation and reward. Conditioned cues associated with reward activate dopamine neurons, and we will determine how these cues affect synaptic responses and cell firing in entorhinal neurons. We will also determine the role of dopamine in controlling the induction of lasting increases and decreases in synaptic strength. Optogenetic stimulation techniques will be used to determine how tonic and phasic synaptic release of dopamine affects excitatory transmission and the excitability of entorhinal neurons. This program of research will determine fundamental neuronal mechanisms through which neuromodulators regulate the circuitry of the entorhinal cortex, to promote sensory processing and mnemonic function.