Hippocampal Inactivation with TTX Impairs Long-Term Spatial Memory Retrieval and Modifies Brain Metabolic Activity

Abstract

Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions.

Dynamics of Goldfish Subregional Hippocampal Pallium Activity throughout Spatial Memory Formation

“…The parahippocampal area of mammals plays a crucial role in spatial memory [Schenk and Morris, 1985;Good and Honey, 1997;Galani et al, 1998;Aggleton et al, 2000Aggleton et al, , 2004Oswald and Good, 2000;Parron and Save, 2004;Hafting et al, 2005;Steffenach et al, 2005;Moser et al, 2008], and imaging studies have shown a persistent activation of these extrahippocampal regions during spatial memory acquisition and on recall [Aggleton et al, 2000;Poirier et al, 2008;Mullally and Maguire, 2011;Epstein and Vass, 2014;Auger et al, 2015;Chadwick et al, 2015]. Like in the present study, sustained spatial learning and memory-related increased oxidative metabolism in the parahippocampal region has been reported in rodents [Matrov et al, 2007;Conejo et al, 2013;Méndez-López et al, 2013]. Thus, the continuous activation observed in the current study in the Dp of goldfish during the acquisition and retrieval stages of a spatial memory task, together with the above mentioned topological and hodological considerations, suggests the alternative possibility that the area Dp could be comparable to the olfactory recipient parahippocampal cortices of mammals and birds.…”

Spatial learning-related changes in metabolic brain activity contribute to the delimitation of the hippocampal pallium in goldfish

“…For example, given that Dlv receives olfactory and other sensory inputs and in turn projects to Dld [5,57,60], it might be considered that at least a part of Dlv (the olfactory bulb recipient zone) could be equivalent to the entorhinal cortex, whereas Dld could correspond to the hippocampus proper. However, although significant increases in brain oxidative metabolism has been observed in the mammalian entorhinal cortex after spatial learning [61], again the absence of involvement of Dld in spatial learning observed not only in the present experiment but also in the lesion experiments above mentioned [14,16] argues also against this possibility.…”

Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task

“…These standards were obtained from Wistar rat brain homogenates of known CO activity determined spectrophotometrically at different thicknesses (10, 30, 50 and 70 m). Following the previously described protocol by Conejo et al [24], the standards were included with each bath of slides. Each set of slides were fixed for 5 min with a 0.5% glutaraldehyde solution, rinsed three times in phosphate buffer and preincubated for 5 min in a solution containing 0.05 M Tris buffer, pH 7.6, with 275 mg/l cobalt chloride 10% (w/v) sucrose and 5 ml of dimethylsulfoxide.…”

“…In addition, these authors suggest that functional interactions among brain regions could be different between control and experimental groups, even when no significant changes are shown in their neuronal activity [45]. As a result, particular regions could be differentially involved at different time points throughout a particular task by changing its interactions with other regions, like the wellknown case of the hippocampus along spatial learning [24,46]. It would be therefore a similar case for the prefrontal cortex during the extinction of spatial memory.…”

“…This technique is useful to measure changes in regional brain activity associated with spatial learning or navigation [19,22,23]. In addition, CO histochemistry has been previously used to assess changes in these functional networks following experimental reversible inactivation [24]. Finally, interregional correlations in CO activity among areas of the medial prefrontal cortex and additional brain regions related with spatial memory extinction will be analyzed to determine functional changes in the neural networks involved in spatial memory extinction after temporal inactivation of the prelimbic area in the prefrontal cortex.…”