Rediscovering area CA2: unique properties and functions

Summary Input-timing dependent plasticity (ITDP) is a circuit-based synaptic learning rule whereby precisely timed, paired activation of direct entorhinal cortex (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of CA1 SC excitation, which has been linked to specificity of contextual memory. We report that paired activation of EC and SC inputs also increases SC excitation of CA2 PNs, which are important for social memory. However, whereas CA1 ITDP depends on endocannabinoid CB1 receptor-dependent long-term depression of feedforward inhibition (iLTD) mediated by cholecystokinin-positive interneurons, CA2 ITDP depends on δ-opioid receptor-dependent iLTD of parvalbumin-positive interneuron inhibition. Blockade of CA2 δ-opioid receptors blocked ITDP and impaired social memory whereas a social encounter with a novel animal decreased CA2 feedforward inhibition and occluded ITDP. Thus, ITDP may provide a more general synaptic learning rule for distinct forms of hippocampal-dependent memory through its recruitment by distinct hippocampal regions.

Section: Resultssupporting

confidence: 93%

Input-Timing-Dependent Plasticity in the Hippocampal CA2 Region and Its Potential Role in Social Memory

Leroy

Brann

Meira

et al. 2017

“…In the stratum oriens (SO) and stratum radiatum (SR) layers, CA1 neurons receive input from CA3 axons (Figure 1A). In addition, about 20% of CA1 SO inputs originate from CA2 axons (Dudek et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Heterophilic Type II Cadherins Are Required for High-Magnitude Synaptic Potentiation in the Hippocampus

Basu

Duan

Taylor

et al. 2017

Summary Hippocampal CA3 neurons form synapses with CA1 neurons in two layers, stratum oriens (SO) and stratum radiatum (SR). Each layer develops unique synaptic properties but molecular mechanisms that mediate these differences are unknown. Here, we show SO synapses normally have significantly more mushroom spines and higher magnitude long-term potentiation (LTP) than SR synapses. Further, we discovered these differences require the Type II classic cadherins, cadherins-6, 9, and 10. Though cadherins typically function via trans-cellular homophilic interactions, our results suggest presynaptic cadherin-9 binds postsynaptic cadherins-6 and 10 to regulate mushroom spine density and high magnitude LTP in the SO layer. Loss of these cadherins has no effect on the lower magnitude LTP typically observed in the SR layer, demonstrating that cadherins-6, 9, and 10 are gatekeepers for high magnitude LTP. Thus, Type II cadherins may uniquely contribute to the specificity and strength of synaptic changes associated with learning and memory.

“…Evidence from functional imaging studies in humans and lesion and recording studies in animals provide different perspectives on whether space and time are processed distinctly or fully integrated within the hippocampal subdivisions. Hippocampal circuitry involves sequential and parallel stages of information processing, such that the entorhinal cortex projects to all hippocampal subdivisions and intrinsic pathways involve successive projections from CA3 to CA2 and CA1, and from CA2 to CA1 (Figure 1; Amaral & Lavenex, 2006; Dudek et al, 2016). Outputs of this circuitry are from CA3 to subcortical areas, and from CA1 back to the entorhinal cortex and other cortical areas both directly and indirectly via the subiculum.…”

Section: Are Time and Space Separated Or Integrated Within The Hippocmentioning

confidence: 99%

On the Integration of Space, Time, and Memory

Eichenbaum

2017

392

329

The hippocampus is famous for mapping locations in spatially organized environments and several recent studies have shown that hippocampal networks also map moments in temporally organized experiences. Here I consider how space and time are integrated in the representation of memories. The brain pathways for spatial and temporal cognition involve overlapping and interacting systems that converge on the hippocampal region. There is evidence that spatial and temporal aspects of memory are processed somewhat differently in the circuitry of hippocampal subregions but become fully integrated within CA1 neuronal networks as independent, multiplexed representations of space and time. Hippocampal networks also map memories across a broad range of abstract relations among events, suggesting that the findings on spatial and temporal organization reflect a generalized mechanism for organizing memories.