Use this URL to cite or link to this record in EThOS:
Title: The role of external tufted cells in activity-dependent plasticity of the olfactory bulb
Author: Hahn, Christiane
ISNI:       0000 0004 7660 3932
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
Neuroplasticity is a feature of the nervous system that allows organisms to adapt to changing environments. Understanding how individual cells in a neural network adjust and integrate their changes to alter circuit function is an important step in elucidating how systems in the brain functionally adapt to a changing sensory world. The olfactory bulb (OB) is a useful model system for studying neuroplasticity because of its stereotyped anatomy and the propensity of many of its components to adjust their properties in an activity-dependent manner. Additionally, inducing changes in OB activity levels can be achieved reliably with straightforward sensory manipulations. In this thesis, we use the OB to explore mechanisms of activity-dependent neuroplasticity on a cellular basis and observe how these adjustments influence the processing output of the network. External tufted cells (ETCs) are excitatory interneurons found in the glomerular layer of the OB and are central to glomerular processing. Olfactory sensory neurons (OSNs) form monosynaptic contacts to ETCs, which drive the glomerular inhibitory circuitry. ETCs further provide a major source of feed-forward excitation to the glomerular output cells, the mitral and tufted cells (M/TCs). Despite their central role in glomerular processing, our knowledge of ETC activity-dependent plasticity is limited. In light of this, we investigated whether sensory experience alters ETC functional and morphological properties and, if so, whether the effects of any adjustments have any effect on glomerular output. We used 24 hours naris occlusion in mice to decrease OB activity. Whole-cell recordings in acute OB slices from control and occluded mice revealed that ETC intrinsic functional characteristics did not change after 24 h occlusion. This was mirrored by a lack of change in their gross morphological features. When input of sufficient strength reaches glomeruli, ETCs and M/TCs are triggered to fire and release glutamate synchronously from their dendrites. This results in the generation of all-or-nothing glutamatergic long-lasting depolarising currents (LLCs), which are crucial for maintaining synchrony in the excitatory glomerular network, and are involved in shaping stimulus-evoked firing output of both ETCs and M/TCs. After short-term sensory deprivation, both ETCs and M/TCs portrayed larger LLCs under certain recording conditions. We demonstrate that OSN release probability does not change with occlusion, and thus likely does not contribute to the LLC phenotype. We also found that auto-evoked glutamatergic excitation in ETCs is not increased after 24 h sensory deprivation. These findings suggest that the locus of the LLC change is elsewhere in the network, potentially in mechanisms that enhance glutamate sensing or release at ETCs and/or M/TCs, and/or in adjustments in the local inhibitory circuitry. To explore whether the synaptic changes we observed with occlusion influence glomerular output, we measured input-output responses by stimulating OSN axons and recording spike responses in ETCs and M/TCs. These experiments revealed that ETCs subtly increase their firing during a stimulus train under occluded conditions when inhibitory signalling is present, whereas M/TCs retain their response profiles both with and without the contribution of inhibitory signalling. Therefore, these properties seem to arise from an intricate interplay of local excitation and inhibition. Our findings reveal that, surprisingly, the intrinsic properties of ETCs remain remarkably stable in response to short-term sensory deprivation despite their central role in glomerular processing. Additionally, we found that glomerular synaptic excitatory drive is enhanced with occlusion, although the mechanisms and implications of this change remain to be explored. This form of activity-dependent plasticity might control the gain of information flow through the circuit, thereby maintaining sensory performance in the face of external perturbations.
Supervisor: Grubb, Matthew Stuart ; Burrone, Juan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available