Bipolar Cells of the Mouse Retina: A Gene Gun, Morphological Study VINCENZO PIGNATELLI AND ENRICA STRETTOI * Istituto di Neuroscienze del Consiglio Nazionale delle Ricerche, sede di Pisa, Area della Ricerca Consiglio Nazionale delle Ricerche, Via Giuseppe Moruzzi 1, 56100 Pisa, Italy ABSTRACT One of the key elements concerning our understanding of the organization of the mouse retina is the complete classification of the various types of bipolar cells. With the present study, we tried to contribute to this important issue. Unfortunately, most of the antibodies that stain specifically bipolar cells in the retina of other mammals hardly work for the retina of the mouse. We succeeded in overcoming this limitation by using a relatively novel tech- nique based on the gene gun transfer of fluorescent dyes to cells. Hence, we were able to stain a considerable number of bipolar cells that could be characterized according to morphological and comparative criteria. We also performed a complete morphometric analysis of a subset of bipolar cells stained by anti–neurokinin-3 receptor antibodies. We found nine types of cone bipolar cells and one type of rod bipolar cell; these data are consistent with the findings of previous studies on the retinas of other mammals, such as rabbits, rats, and monkeys and with a recent study based on the mouse retina (Ghosh et al. [2004] J Comp Neurol 469:70 – 82). Our results also confirm the existence of a common structural similarity among mam- malian retinas. It remains to be elucidated what is exactly the functional role of the various types of cone bipolar cells and what is the specific contribution they provide to the perception of a given visual stimulus. Most probably, each bipolar cell type constitutes a specialized channel for the computation of a selected component of the visual stimulus. More complex signal coding, involving the coordinated activity of various types of bipolar cells, could also be postulated, as it has been shown for ganglion cells (Meister [1996] Proc Natl Acad Sci U S A 93:609 – 614). J. Comp. Neurol. 476:254 –266, 2004. © 2004 Wiley-Liss, Inc. Indexing terms: bipolar cells; gene gun; morphology The central nervous system operates through both se- rial and parallel processing; the latter implicates that multiple, anatomically distinct areas or neural circuits execute various tasks at the same time, upon receiving a similar input signal (Grunert et al., 1994; Prut et al., 2001; Zaborszky, 2002; Chiry et al., 2003; Scott and Johnsrude, 2003). The retina makes no exception to this working strategy: many types of anatomically and functionally dis- tinct ganglion cells, the last neurons in the retinal visual pathway, operate in parallel to provide the brain, through multiple sets of channels, information about the position, chromatic features, contrast, duration, and so on, of a given visual stimulus (Rodieck, 1998). The complexity of ganglion cell physiology originates partly from complex synaptic interactions taking place in the outer and inner plexiform layers of the retina; in turn, the complexity of retinal networks is reflected in the high variety of cellular types that compose each of the various classes of retinal neurons (Masland and Raviola, 2000). In the past few years, the full catalog of neurons has been provided for the retina of various mammals and the puzzle composition is quickly progressing toward the iden- tification of all the retinal cells for an increasing number of species. We know that the rabbit retina (and thus pre- sumably, the retina of most mammals) contains 2 types of photoreceptors, 2 types of horizontal cells, approximately a dozen types of bipolar cells (McGillem and Dacheux, 2001), 23 types of amacrine cells, and, finally, 12 varieties of ganglion cells (Masland, 2001b). Shape, size, pattern of dendritic and axonal stratification, connectivity, staining properties, and so on, contribute to the definition of a cell Grant sponsor: TeleThon Project E833; Grant sponsor: National Insti- tutes of Health; Grant number: R01 EY 12654. *Correspondence to: Enrica Strettoi, Istituto di Neuroscienze del CNR, sede di Pisa, Area della Ricerca, Via G. Moruzzi 1, 56100 Pisa, Italy. E-mail: strettoi@in.cnr.it Received 18 November 2003; Revised 8 March 2004; Accepted 19 April 2004 DOI 10.1002/cne.20207 Published online in Wiley InterScience (www.interscience.wiley.com). THE JOURNAL OF COMPARATIVE NEUROLOGY 476:254 –266 (2004) © 2004 WILEY-LISS, INC.