Abstract
The thalamic midline nucleus reuniens modulates hippocampal CA1 and subiculum function via dense projections to the stratum lacunosum-moleculare (SLM). Previously, anatomical data has shown that reuniens inputs in the SLM form synapses with dendrites of both CA1 principal cells and inhibitory interneurons. However, the ability of thalamic inputs to excite the CA1 principal cells remains controversial. In addition, nothing is known about the impact of reuniens inputs on diverse subpopulations of interneurons in CA1. Therefore, using whole cell patch-clamp electrophysiology in ex vivo hippocampal slices of wild-type and transgenic mice, we measured synaptic responses in different CA1 neuronal subtypes to optogenetic stimulation of reuniens afferents. Our data shows that reuniens inputs mediate both excitation and inhibition of the CA1 principal cells. However, the optogenetic excitation of the reuniens inputs failed to drive action potential firing in the majority of the principal cells. While the excitatory postsynaptic currents were mediated via direct monosynaptic activation of the CA1 principal cells, the inhibitory postsynaptic currents were generated polysynaptically via activation of local GABAergic interneurons. Moreover, we demonstrate that optogenetic stimulation of reuniens inputs differentially recruit at least two distinct and non-overlapping subpopulations of local GABAergic interneurons in CA1. We show that neurogliaform cells located in SLM, and calretinin-containing interneuron-selective interneurons at the SLM/stratum radiatum border can be excited by stimulation of reuniens inputs. Together, our data demonstrate that optogenetic stimulation of reuniens afferents can mediate excitation, feedforward inhibition, and disinhibition of the postsynaptic CA1 principal cells via multiple direct and indirect mechanisms.
Highlights
The thalamic nucleus reuniens (RE) is source of a major extrinsic glutamatergic input to the hippocampus, along with the medial and lateral entorhinal cortices and basolateral amygdala (Dolleman-Van der Weel et al, 1997; Huff et al, 2016; Li et al, 2017)
We examine the physiological consequences of RE inputs in CA1
We show that RE inputs provide a direct, albeit weak monosynaptic excitation as well as a more robust feedforward inhibition via excitation of CA1 interneurons
Summary
The thalamic nucleus reuniens (RE) is source of a major extrinsic glutamatergic input to the hippocampus, along with the medial and lateral entorhinal cortices and basolateral amygdala (Dolleman-Van der Weel et al, 1997; Huff et al, 2016; Li et al, 2017). Previous anatomical tracer studies showed that the RE is reciprocally connected with the hippocampus and medial prefrontal cortex (mPFC) and indicated the existence of a closed loop of information transfer between the mPFC RE CA1→mPFC (Jay and Witter, 1991; Vertes et al, 2007; Hoover and Vertes, 2012). Consistent with the distribution of terminals, direct electrical stimulation of RE was shown to result in a prominent negative field potential or current sink at the SLM (indicative of the location of excitatory synaptic input) and smaller current sources in all other layers of hippocampal CA1 in anesthetized rats (Dolleman-Van der Weel et al, 1997). A subsequent study utilizing similar technique showed that thalamic inputs have comparable ability to excite the CA1 SP as the intrinsic Schaffer collaterals from the contralateral CA3 (Bertram and Zhang, 1999)
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