Feed-Forward and Feed-Back Activation of the Dentate Gyrus In Vivo During Dentate Spikes and Sharp Wave Bursts Markku Penttonen, 1,2 Anita Kamondi, 1 Attila Sik, 1,3 La ´szlo ´ Acsa ´ dy, 1,3 and Gyo ¨rgy Buzsa ´ki 1 * 1 Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, Newark, New Jersey 2 A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland 3 Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary ABSTRACT: Intermittently occurring field events, dentate spikes (DS), and sharp waves (SPW ) in the hippocampus reflect population synchrony of principal cells and interneurons along the entorhinal cortex-hippocam- pus axis. We have investigated the cellular-synaptic generation of D Ss and SPW s by intracellular recording from granule cells, pyramidal cells, and interneurons in anesthetized rats. The recorded neurons were anatomi- cally identified by intracellular injection of biocytin. Extracellular record- ing electrodes were placed in the hilus to record field DSs and multiple units and in the CA1 pyramidal cell layer to monitor SPW-associated fast field oscillations(ripples) and unit activity. DSswere associated with large depolarizing potentials in granule cells, but they rarely discharged action potentials. When they were depolarized slightly with intracellular current injection, bursts of action potentials occurred concurrently with extracel- lularly recorded D Ss. Two interneurons in the hilar region were also found to discharge preferentially with DSs. In contrast, CA1 pyramidal cells, recorded extracellularly and intracellularly, were suppressed during D Ss. In association with field SPW s, extracellular recordings from the CA1 pyramidal layer and the hilar region revealed synchronous bursting of these cell populations. Intracellular recordings from CA3 and CA1 pyramidal cells, granule cells, and from a single CA3 region interneuron revealed SPW-concurrent depolarizing potentials and action potentials. These findings suggest that granule cells may be discharged antero- gradely by entorhinal input or retrogradely by the CA3-mossy cell feedback pathway during DSs and SPWs, respectively. Although both of these intermittent population patterns can activate granule cells, the impact of DSs and SPWs is diametrically opposite on the rest of the hippocampal circuitry. Entorhinal cortex activation of the granule cells during D Ss induces a transient decrease in the hippocampal output, whereas during SPW bursts every principal cell population of the hippo- campal formation may be recruited into the population event. H ippocam- pus7:437–450, 1997. r 1997 Wiley-Liss, Inc. KEY W O RD S: hippocampus; dentate spikes; sharp waves; intracellular recording; pyramidal cells; granule cells; interneurons; network INTRODUCTION The hippocampal formation consists of a complex of three main subfields, the dentate gyrus, the CA3 region, and the CA1 region. Whereas all fields receive direct innervation from the entorhinal cortex, they are gener- ally considered as a series of unidirectionally connected components forming the intrahippocampal ‘‘trisynaptic loop’’ (Amaral and Witter, 1989, 1995; Lopes da Silva et al., 1990). Although the main associational network of the hippocampal formation, the CA3 region, indeed projects heavily to the CA1 field, axon collaterals of CA3 pyramidal cells return to the dentate gyrus where they likely innervate mossy cells, hilar interneurons, and granule cells (Ishizuka et al., 1990; Kunkel et al., 1993; Li et al., 1994; Scharfman, 1994c, Kneisler and Dingle- dine, 1995). T he axons of mossy cells innervate the inner third of the molecular layer of the dentate gyrus both ipsi- and contralaterally and also emit collaterals within the hilus (Amaral, 1978; Laurberg and Sorensen, 1981; Ribak et al., 1985; Buckmaster et al., 1992; Scharfman, 1995). While their primary postsynaptic targets are the dendrites of granule cells, mossy cell collaterals also terminate on hitherto unidentified interneurons (Frotscher and Zimmer, 1983; Ribak et al., 1985; Buckmaster et al., 1992, 1996). T hus, on purely anatomical grounds, one might hypothesize that neuronal information emerging from the recurrent network of the CA3 region is fed back to its main driving input, the dentate gyrus. Previous physi- ological observations lend support to this possibility. Population bursts of CA3 pyramidal cells during hippo- campal sharp waves (SPW) are associated with sinks in *Correspondence to: Gyo ¨ rgy Buzsa ´ki, Center for Molecular and Behavioral, Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ 07102. E-mail: buzsaki@axon.rutgers.edu Accepted for publication 7 April 1997 HIPPOCAMPUS 7:437–450 (1997) r 1997 WILEY-LISS, INC.