Goal-oriented searching mediated by ventral hippocampus early in trial-and-error learning

Abstract

Most behavioral learning in biology is trial and error, but how these learning processes are influenced by individual brain systems is poorly understood. Here we show that ventral-to-dorsal hippocampal subdivisions have specific and sequential functions in trial-and-error maze navigation, with ventral hippocampus (vH) mediating early task-specific goal-oriented searching. Although performance and strategy deployment progressed continuously at the population level, individual mice showed discrete learning phases, each characterized by particular search habits. Transitions in learning phases reflected feedforward inhibitory connectivity (FFI) growth occurring sequentially in ventral, then intermediate, then dorsal hippocampal subdivisions. FFI growth at vH occurred abruptly upon behavioral learning of goal-task relationships. vH lesions or the absence of vH FFI growth delayed early learning and disrupted performance consistency. Intermediate hippocampus lesions impaired intermediate place learning, whereas dorsal hippocampus lesions specifically disrupted late spatial learning. Trial-and-error navigational learning processes in naive mice thus involve a stereotype sequence of increasingly precise subtasks learned through distinct hippocampal subdivisions. Because of its unique connectivity, vH may relate specific goals to internal states in learning under healthy and pathological conditions.

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

“…Our finding, highlighting the importance of GABAergic inhibition for hippocampusdependent memory performance, converges with recent studies in mice reporting learning-related increase of hippocampal inhibitory synapses (Ruediger et al 2012) and impaired memory performance following disruption of hippocampal GABA neuron function by molecular-, opto-or pharmacogenetic approaches (Prut et al 2010;Murray et al 2011;Andrews-Zwilling et al 2012;Caputi et al 2012;Donato et al 2013;Gilani et al 2014;Lovett-Barron et al 2014;Engin et al 2015;Lee et al 2016). Moreover, our findings support recent studies in humans and rodent models linking hippocampal overactivity and hyperexcitability to age-related memory deficits (Koh et al 2010;Bakker et al 2012;Davis et al 2014) and are consistent with the correlation of hippocampal overactivity with memory deficits in schizophrenia (Tregellas et al 2014).…”

Functional organization of the hippocampal longitudinal axis

“…In rodents, ventral, but not dorsal, hippocampal stimulation increases locomotion [117][118] by engaging the NAc and mesolimbic dopamine (DA) system [119][120][121] , whereas inhibiting VH decreases locomotion 104 . This relationship with the NAc is also relevant to the observation that reward-or goal-directed functions localise to ventral parts of rodent hippocampus [122][123] and to the anterior human hippocampus 124 , given that the ventral striatum -in particular the NAc -is considered the 'limbic-motor interface' at which motivation-and emotion-related processing gains access to the motor system [125][126] . The rodent studies discussed above [117][118][119][120][121] examined dorsal vs. ventral functional dissociations, but the anatomical connectivity between the hippocampus and NAc in fact shows a graded topography 39 .…”

Late enrichment maintains accurate recent and remote spatial memory only in aged rats that were unimpaired when middle aged

“…This maximum distance was also assigned to trials in which the distance swam to reach the platform was higher than this distance. The percentage thigmotaxis (percentage time spent in the 10 cm peripheral annulus) and the number of successful trials (i.e., trials in which the rat located the platform) (Ruediger et al 2012) were also computed. For the water maze in Room 2, a short-term (mean of the last two daily trials) and a long-term memory index (mean of the first daily trials) was computed for distance swam to reach the platform from the second to the last training day (adapted from George et al 2006).…”