Brain-derived neurotrophic factor differentially modulates excitability of two classes of hippocampal output neurons.

A R Graves,S J Moore,N Spruston,A K Tryba,C C Kaczorowski

doi:10.1152/jn.00186.2016

Abstract

Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampus-dependent learning and memory. Canonically, this has been ascribed to an enhancing effect on neuronal excitability and synaptic plasticity in the CA1 region. However, it is the pyramidal neurons in the subiculum that form the primary efferent pathways conveying hippocampal information to other areas of the brain, and yet the effect of BDNF on these neurons has remained unexplored. We present new data that BDNF regulates neuronal excitability and cellular plasticity in a much more complex manner than previously suggested. Subicular pyramidal neurons can be divided into two major classes, which have different electrophysiological and morphological properties, different requirements for the induction of plasticity, and different extrahippocampal projections. We found that BDNF increases excitability in one class of subicular pyramidal neurons yet decreases excitability in the other class. Furthermore, while endogenous BDNF was necessary for the induction of synaptic plasticity in both cell types, BDNF enhanced intrinsic plasticity in one class of pyramidal neurons yet suppressed intrinsic plasticity in the other. Taken together, these data suggest a novel role for BDNF signaling, as it appears to dynamically and bidirectionally regulate the output of hippocampal information to different regions of the brain.

Highlights

We show that BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) mediates acute and long-lasting changes in intrinsic neuronal excitability in two classes of subicular pyramidal neurons (EB and LB neurons)
Our study demonstrates that BDNF regulates synaptic plasticity and mediates both acute and long-lasting changes in intrinsic neuronal excitability in two classes of subicular pyramidal neurons (EB and LB neurons)
BDNF plays a similar role in the induction of synaptic plasticity in these two cell types, it differentially and bidirectionally affects intrinsic excitability and burst plasticity in EB and LB neurons

Summary

Introduction

We show that BDNF mediates acute and long-lasting changes in intrinsic neuronal excitability in two classes of subicular pyramidal neurons (EB and LB neurons). The major output pathway of the hippocampus is formed by pyramidal neurons of the subiculum that convey information to downstream target brain areas Lesions of this region have been shown to disrupt performance on hippocampus-dependent learning and memory tasks (Bindu et al 2005). There are two distinct classes of pyramidal neurons in the subiculum, and they differ in their electrophysiological characteristics, morphology, connectivity with other brain regions, and specific requirements for the induction of both synaptic and nonsynaptic (or intrinsic) plasticity (Behr et al 2009; Graves et al 2012; Kim and Spruston 2012; Menendez de la Prida et al 2003; Menendez de la Prida and Gal 2004; Moore et al 2009; Stewart and Wong 1993; Wozny et al 2008). BDNF DIFFERENTIALLY REGULATES HIPPOCAMPAL OUTPUT demonstrate a novel role for BDNF signaling in modulating neuronal function in this critical brain region and suggest that BDNF signaling may act as a switch to direct the flow of hippocampally processed information to specific downstream regions to facilitate the encoding and storage of long-term memories

Methods

Results

Conclusion