Hippocampal subfield‐specific Homer1a expression is triggered by learning‐facilitated long‐term potentiation and long‐term depression at medial perforant path synapses

Abstract

Learning about general aspects, or content details, of space results in differentiated neuronal information encoding within the proximodistal axis of the hippocampus.These processes are tightly linked to long-term potentiation (LTP) and long-term depression (LTD). Here, we explored the precise sites of encoding of synaptic plasticity in the hippocampus that are mediated by information throughput from the perforant path. We assessed nuclear Homer1a-expression that was triggered by electrophysiological induction of short and long forms of hippocampal synaptic plasticity, and compared it to Homer1a-expression that was triggered by LTP and LTD enabled by different forms of spatial learning. Plasticity responses were induced by patterned stimulation of the perforant path and were recorded in the dentate gyrus (DG) of freely behaving rats. We used fluorescence in situ hybridization to detect experience-dependent nuclear encoding of Homer1a in proximodistal hippocampal subfields. Induction of neither STP nor STD resulted in immediate early gene (IEG) encoding. Electrophysiological induction of robust LTP, or LTD, resulted in highly significant and widespread induction of nuclear Homer1a in all hippocampal subfields. LTP that was facilitated by novel spatial exploration triggered similar widespread Homer1a-expression. The coupling of synaptic depression with the exploration of a novel configuration of landmarks resulted in localized IEG expression in the proximal CA3 region and the lower (infrapyramidal) blade of the DG. Our findings support that synaptic plasticity induction via perforant path inputs promotes widespread hippocampal information encoding. Furthermore, novel spatial exploration promotes the selection of a hippocampal neuronal network by means of LTP that is distributed in an experience-dependent manner across all hippocampus subfields. This network may be modified during spatial content learning by LTD in specific hippocampal subfields. Thus, long-term plasticity-inducing events result in IEG expression that supports establishment and/or restructuring of neuronal networks that are necessary for long-term information storage.

The Perirhinal Cortex Engages in Area and Layer-Specific Encoding of Item Dimensions

“…The hippocampal CA1 region plays an important role in the learning about microscale item-place configurations (Kemp and Manahan-Vaughan, 2004;Hagena and Manahan-Vaughan, 2011;Hoang et al, 2018), and the microscale and macroscale behavioral paradigms used in the current study trigger both synaptic plasticity and somatic IEG expression in distinct subcompartments of the hippocampus (Hoang et al, 2018;Hoang and Manahan-Vaughan, 2021). Interestingly, it has been reported that a direct projection from neurons in the superficial layers of the PRC to the CA1 region and more strongly to the subiculum of the hippocampus exists (Naber et al, 1999;Furtak et al, 2007;Agster and Burwell, 2013;Suter et al, 2013).…”

“…The hippocampal dentate gyrus region engages in macroscale item-place encoding (Kemp and Manahan-Vaughan, 2008; Hoang et al, 2018Hoang et al, , 2021. This prompts the question as to whether this process may be supported by macroscale item encoding in area 35.…”

“…This aspect is as yet unclarified. However, it has been reported that novel learning about spatial configurations of large and overt (macroscale) or small and discrete (microscale) objects enables both subregion-specific long-term depression (LTD) and nuclear gene encoding in specific neuronal subcompartments of the hippocampus (Manahan-Vaughan and Braunewell, 1999 ; Kemp and Manahan-Vaughan, 2008 ; Hagena and Manahan-Vaughan, 2011 ; Hoang et al, 2018 , 2021 ).…”

Bidirectional Regulation of Hippocampal Synaptic Plasticity and Modulation of Cumulative Spatial Memory by Dopamine D2-Like Receptors

“…We have recently reported that highly localized gene encoding occurs in the hippocampus during the strengthening of synaptic plasticity by spatial learning (Hoang et al, 2021 ). By contrast, strong afferent protocols that induce highly robust forms of LTP and LTD result in generalized and indiscriminate immediate early gene encoding across the hippocampus (Hoang et al, 2021 ).…”

“…We have recently reported that highly localized gene encoding occurs in the hippocampus during the strengthening of synaptic plasticity by spatial learning (Hoang et al, 2021 ). By contrast, strong afferent protocols that induce highly robust forms of LTP and LTD result in generalized and indiscriminate immediate early gene encoding across the hippocampus (Hoang et al, 2021 ). In this context, it is interesting to note that slow-onset potentiation that is induced by learning activity is impaired in mice that either lack D2R, or undergo local silencing of the receptor in the CA1 region (Espadas et al, 2021 ).…”