The effect of dietary folic acid on mood, cognitive behaviour, and cortical neural activity in healthy rats

Alamir, N. F. (2026) The effect of dietary folic acid on mood, cognitive behaviour, and cortical neural activity in healthy rats. PhD thesis, University of Reading. doi: 10.48683/1926.00129973

Abstract/Summary

Folic acid (FA) plays a key role in one-carbon metabolism, serving as a cofactor in nucleotide and amino acid synthesis, as well as methylation processes. Clinical and observational studies in humans have linked folate deficiency to depression, cognitive decline, and poor response to antidepressant treatment. Animal studies have similarly demonstrated antidepressant- and anxiolytic-like effects of FA, with some evidence of cognitive enhancement, although findings in healthy, non-deficient populations remain inconsistent. Early electrophysiological research reported excitatory effects of folate on cortical neurons but relied on outdated recording technologies and artificial administration routes, limiting their translational relevance. This thesis aimed to address these gaps by investigating the behavioural effects of dietary FA supplementation in healthy rats, and identify any changes in cortical neural activity using in vivo electrophysiological recordings. Healthy male rats were supplemented with FA at 20 mg/kg diet (20 times the recommended dietary allowance) via drinking water for five weeks. Mood and cognitive behaviour were assessed with four tasks: open field test (anxiety-like behaviour), novel object recognition (recognition memory), T-maze delayed alternation (spatial working memory), and beam walking (motor coordination and balance). No significant treatment effects were observed on either mood-related or cognitive behavioural measures. Cortical activity was examined through electrophysiological recordings from the primary barrel cortex under anaesthesia during electrical whisker pad stimulation at four intensities (0.4, 0.6, 0.8, and 1.2 mA). Local field potentials (LFPs) and corresponding current source density (CSD) were analysed for peak amplitude, latency, onset time, and initial slope, and sensory adaptation was assessed with a 10-pulse stimulation paradigm. Resting-state activity was examined via multi-unit activity (MUA) to estimate population spike rates, and Up state initiation dynamics were assessed using LFP, CSD, and MUA measures. FA supplementation significantly increased spontaneous cortical excitability, reflected in elevated firing rates during rest, and accelerated Up state initiation, as indicated by steeper MUA and CSD slopes, and larger MUA peak amplitudes. In contrast, FA did not alter sensory-evoked responses, the relationship between spontaneous and evoked activity, or sensory adaptation. This work provides the first systematic in vivo evidence that dietary FA supplementation enhances spontaneous cortical excitability and modulates Up state initiation dynamics without significantly altering evoked responses or behavioural performance in healthy rats. These findings highlight FA as a promising intervention for modulating cortical activity. Although it did not produce overt behavioural changes in healthy FA-nondeficient rats in this study, FA may potentially serve as a targeted intervention in populations with reduced cortical excitation, such as during ageing, chronic stress, or neuropsychiatric disorders (i.e., major depressive disorder). In such cohorts, shifting cortical dynamics towards excitation may support behavioural improvements, warranting further investigation of dietary FA supplementation as a potential restorative intervention.

Item Type	Thesis (PhD)
URI	https://centaur.reading.ac.uk/id/eprint/129973
Identification Number/DOI	10.48683/1926.00129973
Divisions	Life Sciences > School of Biological Sciences
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