Effects of local inactivations on olivocorticonuclear neuronal activity and memory consolidation.

Simplified views of olivocorticonuclear circuitry involved in motor memory formation, with cortical interneurons, multiple mossy fiber inputs, and some brainstem circuits omitted for clarity. Each panel shows how information transmission and excitabilities within the system may change after different interventions. Excitability increases (↑) and decreases (↓) are indicated. Asterisks denote synapses at which muscimol may be acting. Post-training muscimol infusions to cerebellar cortex (A) prevent consolidation, but it is uncertain whether consolidation processes are disrupted directly in the targeted structure or indirectly through disturbance of the OCN loop. In particular, the excitability of cerebellar nuclear neurons will increase as a consequence of cortical inactivation. However, post-training muscimol infusions to the cerebellar nuclei (B) do not affect consolidation. Nucleo-olivary inhibition is depressed, so olivary excitability will be increased. At Purkinje cells, increased climbing fiber activity increases complex spike activity with a corollary reduction in simple spike activity, indicated by ↑↓, but this does not impair consolidation processes. It remains possible that consolidation occurs entirely in the cerebellar nuclei only if these processes are disrupted by excitability increases, but insensitive deep neuronal inhibition with muscimol. Hence in the present investigation (C), post-training muscimol infusions to both cortex and nuclei cause a deep inhibition of cortical neurons, whilst protecting the cerebellar nuclei from disinhibition. (D) A key to panels A–C and a model of cerebellar pathways engaged in NMR conditioning. CS- and US-related information converges within the cerebellar cortex and within the cerebellar nuclei through mossy fiber and climbing fiber inputs, respectively. The inhibitory olivo-cortico-nuclear loop (OCN) is indicated by dashed arrows. Conventions: excitatory neurons and synapses are shown in white; inhibitory neurons and synapses in black. Abbreviations: Ba, basket cell; cf, climbing fiber; Go, Golgi cell; Grc, granule cell; mf, mossy fibers; NV, trigeminal nucleus; Pc, Purkinje cell; pf, parallel fibers; RN, red nucleus; St, Stellate cell.