Longley, M; (2016) Monoamine influences in cerebellar memory consolidation. Doctoral thesis , UCL (University College London).

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Abstract

An association between climbing fibre and mossy fibre/parallel fibre inputs to the Purkinje cell is critical for cerebellar learning. In addition to these two major afferent systems, the cerebellum also receives a range of neuromodulatory inputs; most prominent are the noradrenergic and serotonergic afferents. Early theoretical and empirical accounts support a role for noradrenergic input as providing an essential third, consolidation signal in learning. In comparison to the glutamatergic afferents very little is known about the anatomy, physiology and behavioural aspects of the neuromodulatory afferents. The distributions by cell type of β1- and β2-adrenoceptors in the cerebellar cortex and nuclei and of α1-adrenoceptors in the cerebellar cortex, are shown for the first time. Earlier work demonstrated the necessity for β-adrenoceptor activation in consolidation of classical conditioning of the nictitating membrane response (NMR). Here, a dissociation of β1- and β2-adrenoceptor expression was shown. β1-adrenoceptors are restricted to Purkinje cells and β2-adrenoceptors are restricted to Bergmann glial cells. The cerebellar cortical distributions of noradrenergic and serotonergic afferents were compared. In cortical vermis, individual noradrenergic afferents were limited in their medial-lateral extent to less than 300 µm but were more extended in the rostral-caudal plane by up to 800 µm. Serotonergic afferents ran orthogonal to the noradrenergic afferents, with extents up to 900 µm in the medial-lateral plane but less than 200 µm in the rostral-caudal plane. Recent work has demonstrated a critical role for Purkinje cell mGlu7 activation in regulating the pause in Purkinje cell simple spike activity believed to be the cellular mechanism underpinning the conditioned eyelid blink/ NMR. Attempts were made to assess the specific function of the β1-adrenoceptor and mGlu7 in consolidation and performance of NMR conditioning, respectively. However, methodological constraints left these questions unresolved. It is concluded that the noradrenaline consolidation signal may target limited cortical territories and modulate Purkinje cells or Bergmann glial cells. In contrast, the serotonin signal is diffuse and targets multiple cortical regions simultaneously to fulfil a role in cerebellar processing distinct from that of noradrenergic signalling.

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