Probing the timeline for the acquisition of altered circuit function in the developing prefrontal cortex

<p>Neurodevelopmental disorders are characterised by cognitive and behavioural deficits, which are underpinned by a broad spectrum of neural deficiencies in brain regions critical for higher-order cognition - more specifically, the medial prefrontal cortex (mPFC). The mPFC is involved in learn...

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Autore principale: Tvrdić, M
Altri autori: Butt, S
Natura: Tesi
Lingua:English
Pubblicazione: 2022
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Riassunto:<p>Neurodevelopmental disorders are characterised by cognitive and behavioural deficits, which are underpinned by a broad spectrum of neural deficiencies in brain regions critical for higher-order cognition - more specifically, the medial prefrontal cortex (mPFC). The mPFC is involved in learning, memory, and decision-making, and its appropriate functioning in adulthood depends on the correct balance between excitation and inhibition established during early neural development.</p> <p>GABAergic interneurons are critical components of cortical circuits where they modulate the firing of neurons and thus control information flow both in adult and developing cortical networks. The early circuits of the mPFC exhibit characteristic discontinuous oscillatory patterns in the beta and gamma frequency ranges. The precise characteristics of these early beta and gamma oscillations are unknown as well as how they relate to the activity of single neurons.</p> <p>Here, we (1) explored the early oscillatory activity in the developing mPFC, (2) we examined the activity of single neurons during development, and (3) we characterised the specific interactions between beta and gamma oscillations and single neurons - with a focus on PV+ and SST+ GABAergic interneurons.</p> <p>We recorded extracellularly from anaesthetised and awake animals and found that anaesthesia affects beta but not gamma oscillations and that both beta and gamma oscillations change over development - with a possible critical period at postnatal day (P) 12. Single neurons were also found to change their features during development and in anaesthesia. Through optotagging, we identified putative SST+ and PV+ interneurons and found that they differentially contribute to beta and gamma activity, as do other single neurons - with a possible critical period also at P12.</p> <p>These findings shed light on the early oscillatory and single neuron activity in the mPFC and inform further investigations on the origins of neurodevelopmental dysfunctions in brain regions critical to higher-order cognition.</p>