Numerous long non-coding RNAs (lncRNAs) play pivotal roles in nervous system development and the modulation of neuronal activity, making them crucial physiological players and potential vulnerability points for neuropsychiatric disorders. MALAT1 stands out as one such lncRNA, exerting control over splicing events by sequestering specific SR-family splicing factors in nuclear inactive compartments such as the nuclear speckles, thereby impeding their action on target transcripts. Notably, nSR100, a member of the SR-family, serves as a key splicing regulator, facilitating the generation of neuroLSD1 through the inclusion of the alternative exon E8a in transcripts encoding Lysine Specific Demethylase 1 (LSD1). Given that LSD1 and neuroLSD1 act as negative and positive modulators, respectively, of plasticity gene expression, their ratio assumes a certain significance in regulating glutamatergic excitability. We postulate that MALAT1 may constitute a novel player in modulating exon E8a inclusion in LSD1 transcripts by sequestering nSR100, thereby influencing the LSD1/neuroLSD1 ratio. Our findings reveal that Malat1 overexpression leads to reduced E8a inclusion in mature LSD1 transcripts, with both events occurring in response to depolarization. Conversely, inhibition of MALAT1 activity prevents depolarization-induced neuroLSD1 downregulation. Furthermore, UV-CLIP experiments demonstrate that the basal interaction between Malat1 and nSR100 is strengthened in response to KCl-induced neuronal activation, implying that this lncRNA could be implicated in sequestering the splicing factor contributing to reducing neuroLSD1 expression. This study sheds light on a novel pathway involved in the regulation of neuronal homeostasis and, potentially, uncovers a new mechanism implicated in disorders characterized by disrupted control of neuronal excitability.