Synaptic integration by different dendritic compartments of hippocampal CA1 and CA2 pyramidal neurons

Abstract

Pyramidal neurons have a complex dendritic arbor containing tens of thousands of synapses. In order for the somatic/axonal membrane potential to reach action potential threshold, concurrent activation of multiple excitatory synapses is required. Frequently, instead of a simple algebraic summation of synaptic potentials in the soma, different dendritic compartments contribute to the integration of multiple inputs, thus endowing the neuron with a powerful computational ability. Most pyramidal neurons share common functional properties. However, different and sometimes contrasting dendritic integration rules are also observed. In this review, we focus on the dendritic integration of two neighboring pyramidal neurons in the hippocampus: the well-characterized CA1 and the much less understood CA2. The available data reveal that the dendritic integration of these neurons is markedly different even though they are targeted by common inputs at similar locations along their dendrites. This contrasting dendritic integration results in different routing of information flow and generates different corticohippocampal loops.

Distribution of interneurons in the CA2 region of the rat hippocampus

“…CA2 interneurons target pyramidal cells locally, as well as in CA1 and CA3 and receive inputs from CA2, CA3, the supramamillary body, the amygdala, the entorhinal cortex and the dentate gyrus (Berretta et al, 2001; Bartesaghi et al, 2006; Chevaleyre and Siegelbaum, 2010; Ding et al, 2010; Piskorowski and Chevaleyre, 2011, 2013; Mercer et al, 2012a,b; Cui et al, 2013; Kohara et al, 2014). These interneurons are therefore ideally located to regulate the network activity and alteration of the inhibitory circuitry in CA2 appears to be linked to some neurological diseases.…”

“…Increasing evidence, however, suggests that the CA2 region is a distinctive subregion that may play a unique role in social memory (Hitti and Siegelbaum, 2014). CA2 pyramidal cells receive Schaffer collaterals inputs (Chevaleyre and Siegelbaum, 2010; Jones and McHugh, 2011), direct input from the entorhinal cortex (Bartesaghi and Gessi, 2004; Bartesaghi et al, 2006; Ding et al, 2010), the amygdala (Berretta et al, 2001), the dentate gyrus (Kohara et al, 2014) and uniquely amongst CA regions, inputs from the supramammillary nucleus, a hypothalamic nucleus thought to be involved in the generation of theta rhythms (Magloczky et al, 1994; Piskorowski and Chevaleyre, 2011; Cui et al, 2013). CA2 has also been shown to project directly to Layer II of the medial entorhinal cortex (MEC) (Rowland et al, 2013).…”

Hippocampal Formation

“…Rather, they combine information from distal CA3 and CA2, perhaps because of the difficulty to separate CA2 as an entity. However, there is growing evidence that CA2 is both anatomically and functionally a distinct region (Chevaleyre and Siegelbaum, 2010;Mercer et al, 2012aMercer et al, , 2012bPiskorowski and Chevaleyre, 2012). Therefore, viewing distal CA3 and CA2 as a homogenous region is no longer tenable.…”

“…Recent evidence indicates that indeed there is a narrow CA2 (∼250 μm), located distal to the end bulb of the mossy fiber projection. This region has connectional and functional differences (Jones and McHugh, 2011;Piskorowski and Chevaleyre, 2012) when compared with the other hippocampal fields. In many respects, CA2 resembles a terminal portion of the CA3 field, yet in other ways CA2 is quite distinct from both CA3 and CA1.…”

New insights into the regulation of synaptic plasticity from an unexpected place: Hippocampal area CA2

“…This property is notable because CA2 is the only region of hippocampus in which afferents originating from projection neurons in both layer II and layer III of the entorhinal cortex terminate, suggesting that the entorhinal cortex may powerfully control the output of CA2 neurons. Such regulation of CA2 output by the entorhinal cortex may have important implications for downstream targets of CA2, mainly pyramidal cells located in area CA1 (Chevaleyre and Siegelbaum 2010;Piskorowski and Chevaleyre 2012). …”