Functional perturbation of forebrain principal neurons reveals differential effects in novel and well-learned tasks

Abstract

Neural circuits in mammalian brains consist of large numbers of different cell types having different functional properties. To better understand the separate roles of individual neuron types in specific aspects of spatial learning and memory, we perturbed the function of principal neurons in vivo during maze performance or in hippocampal slices during recording of evoked excitatory synaptic potentials. Transgenic mice expressing the Drosophila allatostatin receptor (AlstR) in cortical and hippocampal pyramidal cells were tested on an elevated plus maze, in a Y-maze, and in the Morris water maze. Relative to a control cohort, AlstR-positive mice treated with allatostatin exhibited no difference in open arm dwell time on the elevated plus maze or total number of arm entries in a Y-maze, but displayed reduced spontaneous alternation. When animals received massed or spaced training trials in the Morris water maze, and the peptide was delivered prior to an immediate probe, no effects on performance were observed. When the peptide was delivered during a probe trial performed 24 h after seven days of spaced training, allatostatin delivery to AlstR positive mice enhanced direct navigation to the escape platform. Combined, these results suggest that cortical and hippocampal pyramidal neurons are required during spatial decisionmaking in a novel environment and compete with other neural systems after extended training in a long-term reference memory task. In hippocampal slices collected from AlstR positive animals, allatostatin delivery produced frequency dependent alterations in the Schaffer collateral fiber volley (attenuated accommodation at 100 Hz) and excitatory postsynaptic potential (attenuated facilitation at 5 Hz). Combined, the neural and behavioral discoveries support the involvement of short-term plasticity of Schaffer collateral axons and synapses during exploration of a novel environment and during initial orientation to a goal in a well-learned setting.

The puzzle of spontaneous alternation and inhibition of return: How they might fit together

“…Lesions to the anterior thalamic nuclei (Aggleton & Nelson, ), fornix (Dumont, Amin, Wright, Dillingham, & Aggleton, ) and the prelimbic region of the medial prefrontal cortex (Delatour & Gisquet‐Verrier, ), as well as disruption to the cerebellum via genetic mutation (Lalonde, Joyal, Cote, & Botez, ) impair many aspects of spatial learning (and nonspatial learning)—including those measured by spontaneous alternation. As noted by O'Keefe and Nadel (), the region most readily associated with spatial tasks, the hippocampus, is critical for spontaneous alternation behavior: lesions to the hippocampus eliminate spontaneous alternation (e.g., Stoneham et al, ), and promotion of neuroplasticity or signalling within the hippocampus increases spontaneous alternation (e.g., Cao et al, ).…”

Propionic acid ameliorates cognitive function through immunomodulatory effects on Th17 cells in perioperative neurocognitive disorders

“…Hippocampus is also crucial to the generation of spontaneous alternation behavior. Research shows that hippocampal injury can reduce spontaneous alternation behavior [ 38 ], but the enhancement of neuroplasticity or signal in the hippocampus can increase spontaneous alternation behavior [ 39 ]. Our Y-maze test results indicated that PA pretreatment can improve the reduction of spontaneous alternation behavior caused by surgery.…”

Erratum

“…As noted by O' Keefe and Nadel (1978), the region most readily associated with spatial tasks, the hippocampus, is critical for spontaneous alternation behavior: lesions to the hippocampus eliminate spontaneous alternation (e.g., Stoneham et al, 2017), and promotion of neuroplasticity or signalling within the hippocampus increases spontaneous alternation (e.g., Cao et al, 2018).…”