Masters work

Here is a brief summary of the Neuroscience masters projects that I undertook:

Receptor pharmacology of gamma oscillations induced in the Avian Hippocampus in vitro

Introduction: Gamma rhythms are a physiological feature of the mammalian hippocampus and play an important role in memory processing. However, such oscillations have not been explored in the avian hippocampal formation (HF) whose neuroanatomy is unlike its mammalian counterpart. We therefore investigate how divergent structures perform convergent functions. If similar micro-circuitry underlies the avian HF, then we would predict that similar network properties should be detectable.

Aims: We investigate the existence of gamma oscillations in avian HF, the underlying mechanisms of rhythmogenesis and the role of different receptors in this activity.

Methods: We euthanized newly hatched chicks by cervical dislocation. We employed in vitro electrophysiology to record local field potentials in chick brain slices (400 µm). Bath application of various agonists and antagonists allowed us to elucidate the receptor pharmacology of avian hippocampal gamma oscillations in vitro.

Results: In P0 - P4 chick HF brain slices, persistent gamma frequency oscillations (peak power: 64 ± 24.8 µV2/Hz; peak frequency: 36 ± 1.4 Hz; n = 27 slices) were induced by the bath application of the cholinergic agonist, carbachol (10 µM). However, the bath application of kainate (50 - 800 nM), a glutamate receptor agonist, did not elicit gamma. Similar to other species, carbachol-evoked gamma oscillations were sensitive to GABA-A, AMPA/kainate and muscarinic (M1) receptor antagonism.

Conclusions: We conclude that in juvenile chick HF, gamma rhythmogenesis is cholinergic in nature. This is unlike in adult mammals where both cholinergic and glutamatergic mechanisms are known to exist. However, similar to mammalian species, muscarinic acetylcholine receptor (mAChR) activated avian HF gamma oscillations are likely to arise via a pyramidal-interneuron gamma (PING) based mechanism.

Here is a poster about this work

Avian_gamma_Poster_v1.1.pdf

This work was published after peer-review: Dheerendra, P., Lynch, N.M., Crutwell, J., Cunningham, M.O. and Smulders, T.V., 2018. In vitro characterization of gamma oscillations in the hippocampal formation of the domestic chick. European Journal of Neuroscience, 48(8), pp.2807-2815.

https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.13773

Dheerendra_et_al-2018-European_Journal_of_Neuroscience.pdf

Spatial distribution of spike-related slow potentials in primate motor cortex

Introduction: A recent study [1] in primate motor cortex has described features in the low-frequency local field potential (lf-LFP) that are time-locked to neuronal firing (so-called ‘spike-related slow potentials’, SRSPs). SRSPs associated with a single neuron exhibited considerable variation in shape, amplitude and polarity across LFPs recorded on other electrodes. We speculate that this variability reflects spatially-distinct spike-related sources arising from synaptic currents associated with the network in which the neuron is embedded.

Aims: We examined the spatial distribution of SRSPs in order to investigate their physiological basis and to inform the design of recording arrays optimised for extracting signals for LFP-based Brain-Machine Interfaces (BMIs).

Methods: We recorded from 12 moveable microwire electrodes implanted in the primary motor cortex of a macaque. In addition, we used two linear microelectrode arrays (LMAs; 16 channels, 0.5mm spacing), implanted through the bank of the central sulcus and the convexity of the pre-central gyrus respectively, to provide a spatial profile of the LFP.

Results: We calculated SRSPs by fitting a multiple-input multiple output model relating firing rates to lf-LFPs [1]. Principal Component Analysis (PCA) suggested that the variability in SRSP waveform was greatest across microwires and across the sulcal LMA, while the gyral LMA exhibited stereotyped SRSPs. In general >90% of the variability of SRSPs recorded from the gyrus was explained by a single PC. Across both LMAs and microwire recordings, three PCs were able to capture ~98% of the total SRSP variability.

Conclusions: These findings suggest that using electrodes targeting specific depths within the bank of the central sulcus may minimise the redundancy (hence maximise the information content) of the recorded lf-LFPs. A reduction in the number of channels required, alongside our use of low frequency signals, may enable recording and signal-processing using low-power electronics. This has important implications for the development and miniaturisation of robust, low-power BMIs for human patients.

[1] Hall TM, Nazarpour K, Jackson A (2014), Real-time estimation and biofeedback of single neuron firing rates using local field potentials. Nature Communications

Here is a poster about this work

BMI_poster_v6.pdf