In mammals, spatial learning and memory depend on neural processing carried out in the hippocampal formation. Interestingly, extracellular recordings from behaving animals have shown that cells in this region exhibit spatially modulated activity patterns, thus providing insights into the neural activity underlying spatial behaviour. One area within the hippocampal formation, layer II of the medial entorhinal cortex, houses cells that encode a grid-like map of space using a firing rate code. At the same time, oscillatory signals at distinct theta (4–12 Hz) and gamma (30–120 Hz) frequencies are also present in layer II, providing a substrate for a timing code. To understand how layer II of the medial entorhinal cortex produces these outputs I sought to characterise the electrical properties and functional computational architecture of its microcircuitry. The functionality of any neural circuit depends on the electrical properties of its constituent cells. Because the grid cells in layer II are likely to be stellate cells, I used the perforated patch-clamp technique to accurately assess the intrinsic excitable properties of this cell type. Compared to whole-cell recordings, these recordings indicate that some intrinsic properties of stellate cells, such as spike clustering, which is revealed to be robust, are more likely to play a functional role in circuit computation. Conversely, other intrinsic properties, such as spontaneous membrane potential fluctuations, which are confirmed to be insufficiently stable to support reliable interference patterns, are revealed to be less likely than other, more robust electrical properties to play a direct role in circuit function. The characteristic connectivity profiles of different cell types are also critical for circuit function. To investigate cell type-specific connectivity in layer II I used optogenetic stimulation in combination with in vitro electrophysiology to record synaptic activity in different cell types while selectively activating distinct subpopulations of cells with light. Using this method I found that connections between stellate cells are absent or very rare and that communication between stellate cells is instead mediated by strong feedback inhibition from fast-spiking interneurons. Dissecting oscillatory activity in neural circuits may be important for establishing functionally relevant circuit architecture and dynamics but is difficult in vivo. I accomplished this in vitro by recapitulating the interacting theta and gamma rhythms that are observed in vivo with an optogenetic method. I found that locally driving a subset of neurons in the layer II microcircuit at theta frequency with a light stimiulus produced a nested field rhythm at gamma frequency that was also evident as rhythmic inhibition onto stellate cells. Critically, these interacting rhythms closely resembled those recorded from behaving animals. In addition, I found that this thetanested gamma is sufficiently regular to act as a clock-like reference signal, indicating its potential role in implementing a timing code. To functionally dissect the circuit I performed multiple simultaneous whole-cell patch-clamp recordings during circuit activation. These recordings revealed how feedback interactions between stellate cells and fast-spiking interneurons underpin the theta-nested gamma rhythm. Together, these results suggest that feedback inhibition in layer II acts as a common substrate for theta-nested gamma oscillations and possibly also grid firing fields, thereby providing a framework for understanding how computations are carried out in layer II of the medial entorhinal cortex.

The subfornical organ (SFO) is an area in the brain characterized by lack of a blood-brain-barrier that contributes to interaction between the circulation and the central nervous system, and plays key roles in regulation of energy balance. The SFO has two subregions- the dorsolateral peripheral SFO (pSFO) and the ventromedial core of the SFO (cSFO). This study demonstrated the expression of voltage-gated Na+ channel 1.3 (Nav1.3) in the SFO neurons, and a higher Nav1.3 expression in the pSFO. Based on the Nav1.3 expression pattern, intrinsic electrophysiological properties were compared between cSFO and non-cSFO neurons (putative pSFO neurons) identified by a SmartFlare mRNA probe. The patch clamp results revealed a bursting firing pattern in cSFO neurons and a higher spontaneous neuronal activity in non-cSFO neurons. The higher neuronal activity might be related to a more depolarized resting membrane potential and a higher trend of Na+ current density.

Younger siblings of children with autism (Sibs-ASD) are at risk for the development of an Autism Spectrum Disorder (ASD) or subclinical social and cognitive deficits better known as the Broader Autism Phenotype (BAP).The current study utilized a multi-level approach to examine executive attention and social competence in preschool-aged Sibs-ASD and a comparison group of age-, sex-, and Verbal IQ-matched younger siblings of children without autism (Sibs-COM). Forty-two participants (24 Sibs-ASD, 18 Sibs-COM) completed a modified version of the Children’s Attention Network Task (ANT), with electroencephalograph (EEG) collected simultaneously, and a peer interaction paradigm with an unfamiliar peer.Overall, Sibs-ASD and Sibs-COM displayed comparable performance on behavioral indices of the Children’s ANT, P3 amplitude and latency, and measures of observed social functioning. Surprisingly, Sibs-ASD displayed a reduced (less negative) N2 amplitude and shorter N2 latency, most evident at Fz compared to FCz, a finding not observed in Sibs-COM. Furthermore, on a parent-report index of social functioning,Sibs-ASD reportedly displayed greater social impairments than Sibs-COM. Interestingly, post-hoc analyses indicated that differences in N2 amplitude and social functioning were most apparent between affected Sibs-ASD and Sibs-COM. Therefore, results of this study provide support for social and cognitive deficits consistent with theories of the BAP.

The difficulty with movement initiation, or akinesia, is a cardinal symptom of Parkinson�s disease (PD) and the loss of dopaminergic cells, affecting the function of the basal ganglia, the thalamus and the motor cortex, has long been documented. From a broader perspective, it has been proposed that akinesia is caused by impaired function in different brain areas, inside and outside the basal ganglia, operating as a �behavioural arrest control system� (Klemm, 2001). Several neurotransmitters seem to modulate the activity of this system and, contrasting the well-known effects of dopamine, the involvement of adenosine has only recently emerged, particularly via A2A receptors. Adenosine plays an opposite role to dopamine in the brain: adenosine stimulation at A2A receptors inhibits movement (Ferre et al., 1991a; Hauber and Munkle, 1995; Rimondini et al., 1997), whereas A2A antagonists seem to promote movement (Kanda et al., 2000; Bara-Jimenez et al., 2003; Pinna et al., 2005). Although specific adenosine A2A and dopamine D2 receptors are known to antagonistically interact (Ferre et al., 1997; Fuxe et al., 1998; Ferre et al., 2001), little is known of the involvement of A2A receptors in regulating neural activity in the basal ganglia, a crucial point for the future use of A2A antagonists as adjuvant therapy in Parkinson�s disease. In fact, although it is generally accepted that akinesia results from altered function in the cortico-basal ganglia-cortical loop, as confirmed in several studies reporting changes in basal ganglia activity following dopamine depletion (Blandini et al., 2000; Bevan et al., 2002; Boraud et al., 2002), no study to date has systematically investigated electrophysiological changes in the basal ganglia during akinesia induced by adenosine receptor stimulation. Starting from a common behavioural effect, this study tries to bridge this gap by investigating and comparing, in two basal ganglia structures, the neural substrate of akinesia after acute dopamine D2 receptor blockade and adenosine A2A receptor stimulation. The external segment of the globus pallidus (GP, or simply globus pallidus in the rat) and the substantia nigra pars reticulata (SNr) were chosen as the recording sites because both nuclei are included into the �behavioural arrest control system� and seem to express somewhat complementary functions, as a respective key integrative station and main output of the basal ganglia. Dopamine function was manipulated by acute decrease in availability of dopamine binding sites in the brain, through specific dopamine D2 receptor blockade with systemic injections (1.0 and 1.5 mg/kg) of raclopride(3,5-dichloro-N-[(1-ethylpyrrolidin-2-y)methyl]-2-hydroxy-6-methoxy-benzamide), resulting in akinesia. Conversely, movement was inhibited by specific adenosine A2A receptor stimulation with systemic injections (2.5 and 5.0 mg/kg) of the drug CGS21680 (sodium-2-p-carboxyethylphenylamino-5-N-carboxamidoadenosine). In both situations, behaviour was assessed through specific akinesia tests. Single neuron activity before injection and changes in the firing frequency and firing pattern occurring after injection have been analysed and compared for each cell recorded from GP and SNr, during periods of behavioural rest. Synchronised firing between cell pairs has also been assessed. However, the small number of cell pairs showing correlated firing in each structure after systemic injection of drugs was not statistically relevant for further analysis and interpretation of synchronised firing during drug induced akinesia. In our experiments, both drugs inhibited movement, albeit somewhat differently, with lack of rigidity and �flat� body position after adenosine stimulation. Dopamine blockade decreased mean firing rate and dramatically altered the firing pattern in both investigated structures, generally increasing burst activity (increased percentage of spikes in bursts, mean number of bursts, mean number of spikes per burst, mean intra-burst firing frequency) and decreasing regularity of firing (increased coefficient of variation of the inter-spike intervals). Increased burst activity in the rat basal ganglia in an acute model of parkinsonian akinesia, following systemic raclopride injections, confirmed the importance of changes in the firing pattern in PD. The only electrophysiological effect of systemic A2A stimulation was decreased mean firing rate in the GP, a weak effect that could not propagate towards output stations of the basal ganglia. The lack of changes in the firing pattern, at both input and output levels of the basal ganglia, suggests a correlation with the lack of rigidity in adenosine-stimulation-induced akinesia.

Some patients suffer hearing loss in the early postoperative period following vestibular schwannoma (VS) excision despite having intact hearing immediately after surgery. As this phenomenon has rarely been documented or described, the putative mechanism remains vague. The objective of the current study was to document the patterns of change in behavioural and electrophysiological responses in patients following VS surgery to better describe the phenomenon of delayed hearing loss. In particular, we aimed to determine whether the impairment that eventually leads to delayed hearing loss is neural or cochlear in origin. Auditory function was monitored in six adult patients who underwent surgery at Christchurch Public Hospital for excision of unilateral vestibular schwannoma through the retrosigmoid approach. Patients were assessed pre- and postoperatively by puretone audiometry, speech audiometry, tympanometry, distortion product otoacoustic emissions (DPOAEs), and auditory brainstem response (ABR). When measurable hearing was demonstrated postoperatively, pure-tone audiometry, speech audiometry and ABR were assessed at 24 hour intervals following surgery. Transtympanic electrocochleography (ECochG) was carried out if wave I of the ABR was lost during the postoperative period. Postoperative monitoring revealed that 4 patients suffered permanent anacusis and the remaining 2 patients had permanent hearing preservation. There were no patients who experienced delayed hearing loss in the early postoperative period. A phenomenon similar to delayed hearing loss was observed in case 2 who demonstrated loss of ABR wave I on the 7th postoperative day. Postoperative ECochG recorded in this case showed an enhanced negative SP on the operated side. The findings of this study are discussed in detail with particular reference to the underlying pathophysiology.

Thesis (Ph. D.)--University of California, San Diego, 2007. / Title from first page of PDF file (viewed October 5, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

Thesis (D.M.)--University of Adelaide, 1986. / Includes bibliographical references (leaves 156-173).

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: Phillip J. Holcomb. Submitted to the Dept. of Psychology. Includes bibliographical references (leaves 123-135). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available in print.

Thesis (Ph.D.)--University of Wollongong, 2003. / Typescript. Includes appendices. Embargo in place till November 2005. Bibliographical references: leaf 249-276.