Dendritic Morphology of an Inhibitory Retinal Interneuron Enables Simultaneous Local and Global Synaptic Integration

Abstract

Amacrine cells, inhibitory interneurons of the retina, feature synaptic inputs and outputs in close proximity throughout their dendritic trees, making them notable exceptions to prototypical somato-dendritic integration with output transmitted via axonal action potentials. The extent of dendritic compartmentalization in amacrine cells with widely differing dendritic tree morphology, however, is largely unexplored. Combining compartmental modeling, dendritic Ca 21 imaging, targeted microiontophoresis and multielectrode patch-clamp recording (voltage and current clamp, capacitance measurement of exocytosis), we investigated integration in the AII amacrine cell, a narrow-field electrically coupled interneuron that participates in multiple, distinct microcircuits. Physiological experiments were performed with in vitro slices prepared from retinas of both male and female rats. We found that the morphology of the AII enables simultaneous local and global integration of inputs targeted to different dendritic regions. Local integration occurs within spatially restricted dendritic subunits and narrow time windows and is largely unaffected by the strength of electrical coupling. In contrast, global integration across the dendritic tree occurs over longer time periods and is markedly influenced by the strength of electrical coupling. These integrative properties enable AII amacrines to combine local control of synaptic plasticity with location-independent global integration. Dynamic inhibitory control of dendritic subunits is likely to be of general importance for amacrine cells, including cells with small dendritic trees, as well as for inhibitory interneurons in other regions of the CNS.

Functional properties of GABAA receptors of AII amacrine cells of the rat retina

“…All cells (both whole-cell and patch recordings) were imaged with wide-field fluorescence microscopy after recording to confirm the identity of the cell. For some cells we acquired a series of fluorescence images at closely spaced focal planes using a digital CCD camera, either a CoolSnap ES (Photometrics/Roper Scientific) controlled by µManager software ( www.micro-manager.org ) or an Imago QE controlled by TILLvisION software (TILL Photonics), for details see ( 40 ). Subsequently, images were processed with Huygens (64 bit, Windows; Scientific Volume Imaging) to remove noise and reassign out-of-focus light by deconvolution with a theoretical point-spread function (CMLE method).…”

Spatial integration of dendrites in fast-spiking basket cells

“…Sodium ion channels and NMDA receptors are the main amplification mechanism for supralinear integration of pyramidal neurons (Nevian et al, 2007 ). Alike, dendritic properties such as fast inactivating K + current (Shibata et al, 2000 ) and dendritic morphology (Hartveit et al, 2022 ), or synaptic conductances can affect spatial integration and the first spike latency, which together provide precise mediation of the postsynaptic neurons.…”