Small lesions of the dorsal or ventral hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval, and combining them attenuates the acquisition rate of spatial reference memory

Abstract

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over‐generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.

Septotemporal variation in modulation of synaptic transmission, paired-pulse ratio and frequency facilitation/depression by adenosine and GABAB receptors in the rat hippocampus

“…Recent evidence shows that neuromodulation play significant roles in diversifying the functions of the local neuronal network along the hippocampus ( Dubovyk and Manahan-Vaughan, 2018 ; Grigoryan and Segal, 2013 ; Maggio and Segal, 2007 ; Malik and Johnston, 2017 ; Mlinar and Corradetti, 2018 ; Papaleonidopoulos et al, 2018 ; Reis et al, 2019 ). Interestingly, working memory which may engage changes in short-term synaptic plasticity ( Devaraju et al, 2017 ; Le Barillier et al, 2015 ; Pals et al, 2020 ) and is amenable to neuromodulation ( Cardoso-Cruz et al, 2014 ; McHugh et al, 2008 ) may involve a distinct participation of the dorsal (posterior) and ventral (anterior) hippocampus, as recent evidence suggests ( Hauser et al, 2020 ; Li et al, 2022 ). However, despite the plethora of evidence regarding dorsoventral differences in short-term synaptic plasticity, little is known regarding the actions of neuromodulation on short-term synaptic plasticity along the hippocampus.…”

Altered Functional Connectivity of Insular Subregions in Type 2 Diabetes Mellitus

“…The hippocampus is responsible for memory, including working memory and episodic memory ( Banquet et al, 2020 ). Studies show that the hippocampus is mainly involved in retrieval of working memory ( Oztekin et al, 2009 ; Hauser et al, 2020 ), and the dAI is significantly activated in working memory tasks ( Barber et al, 2013 ) and plays an important role in updating incremental working memory ( Halahalli et al, 2015 ). Working memory is one of the most vulnerable cognitive domains in patients with T2DM ( Sadanand et al, 2016 ).…”

Hippocampal Sclerosis in Pilocarpine Epilepsy: Survival of Peptide-Containing Neurons and Learning and Memory Disturbances in the Adult NMRI Strain Mouse

“…Similar (although less dramatic) impairment of spatial learning was seen after kainic acid lesions of the CA1 sector of the dorsal hippocampus in mice [ 52 ]. The non-epileptic experimental lesions of the dorsal and ventral hippocampus are also associated with impairments in working memory and reference memory retrieval [ 53 ]. A similar spatial memory disturbance occurred following the lesion of the lateral entorhinal cortex in our previous experiments [ 54 ].…”