No description available.

Recent anatomical investigations have revealed that the striatum is an intrinsically heterogeneous structure that forms multiple parallel circuits with different cortical areas. The present series of experiments investigated the possibility that such anatomical diversity may promote functional differences between subregions of the rat dorsal striatum. Using different versions of the water maze and radial arm maze tasks, evidence is presented showing that the medial and lateral subregions of the caudate-putamen make distinct contributions to behaviors guided by either ambient spatial or discrete cues. The findings support a multiple subsystems view of dorsal striatal function. Specifically, the lateral (sensorimotor-innervated) caudate-putamen may mediate the process of habit formation based on simple stimulus-response associations, whereas the medial (limbic-innervated) caudate-putamen may contribute to the cognitive/spatial control of behavior in competitive response situations. Further evidence is presented suggesting that the medial caudate-putamen is functionally related to the hippocampal system. Together, these structures may form a functional limbic circuit that mediates the serial processing of cognitive/spatial information.

No description available.

The striatum is the major input structure of the basal ganglia, and is composed of two major populations of spiny projection neurons (MSNs), which give rise to the socalled direct and indirect pathways, and several types of interneuron. Dopaminergic inputs to striatum are critical for its proper function. Indeed, loss of dopaminergic neurons in Parkinsonism leads to motor disturbances, grossly disturbs striatal activity, and is associated with the emergence of excessively-synchronized network oscillations at beta frequencies (15-30 Hz) throughout the basal ganglia. How the distinct structural, neurochemical and other properties of striatal neurons are reflected in their firing rates and patterns in vivo is poorly defined, as are their possible cell-type-selective contributions to the aberrant oscillations arising in the Parkinsonian brain. To address these issues, I first used multi-electrode arrays to record the spontaneous firing of ensembles of neurons in dorsal striatum in both anaesthetised dopamine-intact and Parkinsonian (6-hydroxydopamine-lesioned) rats during two well-defined brain states, slow-wave activity (SWA) and spontaneous activation. The chronic loss of dopamine led to an overall increase in the average firing rates of striatal neurons, irrespective of brain state. However, many neurons in the Parkinsonian striatum still exhibited the low firing rates and irregular firing patterns typical of neurons in the dopamine-intact striatum. During SWA in Parkinsonian rats, the firing of striatal neurons was more strongly synchronized at low frequencies, in time with cortical slow (~1 Hz) oscillations. During spontaneous cortical activation in Parkinsonian rats, more striatal neurons engaged in synchronized firing in time with cortical beta oscillations. Under the same experimental conditions, I then recorded the spontaneous firing of individual striatal neurons and juxtacellularly labelled the same neurons to verify their cell types, and locations; indirect pathway and direct pathway MSNs were distinguished by the expression (and lack of expression respectively), of the neuropeptide precursor preproenkephalin (PPE). After chronic dopamine loss, and on average, only indirect pathway (PPE+) MSNs significantly increased their firing rates during both brain states, and engaged in widespread, synchronized firing in the beta-frequency range. This did not hold true for all PPE+ MSNs; the Parkinsonian striatum contained many MSNs that were virtually quiescent, which were just as likely to belong to the indirect pathway as the direct pathway. Direct pathway (PPE-) MSNs increased their firing only during SWA after chronic dopamine loss and rarely engaged in aberrant beta oscillations. Taken together, these data suggest that (1) the firing patterns, as well as the firing rates of many striatal neurons are grossly disturbed by chronic loss of dopamine and (2) that the pathological synchronization of the rhythmic firing of a subpopulation of indirect pathway MSNs could contribute to the propagation of aberrant beta-frequency oscillations to downstream basal ganglia nuclei in Parkinsonism.

No description available.

The basal ganglia are a collection of sub-cortical nuclei involved in the execution of a range of motor and cognitive behaviours. The striatum is the input nucleus of the basal ganglia, receiving major excitatory innervation from the cerebral cortex and intralaminar thalamic nuclei. The main target of these two pathways are the principal striatal neurons, the medium-sized spiny neurons (MSNs), which are subdivided based on their axonal targets and the expression of molecular markers. Direct pathway neurons project to the output nuclei of the basal ganglia and express the D, dopamine receptor subtype, whereas indirect pathway MSNs project to the output nuclei via the globus pallidus, and express the D2 receptor. The striatum also contains interneurons that are essential in processing information within striatum; the cholinergic interneuron is of particular interest due to its role in reward-related behaviour. The aim of this study was to examine the cortical and thalamic innervation of subtypes of striatal neurons. To examine whether the cortical or thalamic afferents selectively innervate direct or indirect pathway neurons, transgenic mice expressing GFP under either the D, or D2 receptor promoter were used. Striatal sections from these mice were immunostained to reveal the GFP and selective markers of the cortical and thalamic afferents, VGluTI and VGluT2, respectively. A quantitative electron microscopic examination ofsynaptic connectivity was carried out. The results indicate that there is no selectivity of either the cortical or thalamic pathway for D, or D2 expressing MSNs. Thus both direct and indirect pathway MSNs are involved in the processing of both cortical and thalamic information The cortical and thalamic innervation to cholinergic interneurons was also examined. Stimulation of cortex and thalamus in vivo in anaesthetised rats resulted in short-latency excitatory responses in identified cholinergic interneurons, indicative of monosynaptic connections. After recording, cholinergic interneurons were filled with neurobiotin. The synaptic innervation from cortex and thalamus was then examined in two individual, electrophysiologically characterised, and neurochemically identified cholinergic interneurons. One neuron received input from both cortex and thalamus, whereas the other neuron received input from the thalamus only. These results provide anatomical and physiological data illustrating how the excitatory inputs to striatum innervate cholinergic interneurons.

This research seeks to pinpoint the telencephalic structures most closely correlated with feeding flexibility, which is operationalised as feeding innovation rate per taxon. By calculating a weighted average per taxon of 1030 feeding innovations collated from five zones of the world (western Europe, North America, Australia, New Zealand and India), the study shows that relative size of the hyperstriatum ventrale and, to a lesser extent, the neostriatum , best predicts weighted innovation rate; these two structures are thought to be functionally equivalent to the mammalian neocortex. The worst telencephalic predictors of innovation rate are two structures respectively thought to be involved in primary visual projection and the control of stereotyped, species-specific behaviour, the wulst area and the paleostriatum. / A second presumed correlate of behavioural flexibility, taxonomic variation in the use of urbanised and other anthropogenically-modified habitats, shows a consistent pattern in four geographical zones (Great Britain, North America, Australia and New Guinea), as well as a qualitative association with the relative size of the forebrain. There is no linear correlation, however, between urbanisation rate per taxon and either forebrain size or innovation rate, suggesting that other variables like diet, tameness and neophilia may have to be quantified at finer taxonomic levels in future studies of opportunism in habitat use.

Thesis (Ph. D.)--University of California, San Diego, 1997. / Vita. Includes bibliographical references (leaves 174-188).

Striatal oscillatory activity associated with movement, reward, and decision-making is observed in several interacting frequency bands. Rodent striatal local field potential recordings show dopamine- and reward-dependent transitions between a 'spontaneous' state involving beta (15-30 Hz) and low gamma (40-60 Hz) and a 'dopaminergic' state involving theta (4-8 Hz) and high gamma (60-100 Hz) activity. The mechanisms underlying these rhythmic dynamics and their functional consequences are not well understood. In this thesis, I construct a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms as well as their modulation by dopamine and rhythmic inputs, and test its predictions using human electroencephalography (EEG) data. Chapter 1 describes the striatal model and its dopaminergic modulation. Building on previous work suggesting striatal projection neuron (SPN) networks can generate beta oscillations, I construct a model network of striatal fast-spiking interneurons (FSIs) capable of generating delta/theta (2-6 Hz) and gamma rhythms. This FSI network produces low gamma oscillations under low (simulated) dopaminergic tone, and high gamma activity nested within a delta/theta oscillation under high dopaminergic tone. In a combined model under high dopaminergic tone SPN network beta oscillations are interrupted by delta/theta-periodic bursts of gamma-frequency FSI inhibition. This high dopamine-induced periodic inhibition may enable switching between beta-rhythmic SPN cell assemblies representing motor programs, suggesting that dopamine facilitates movement in part by allowing for rapid, periodic changes in motor program execution. Chapter 2 describes the model's response to square-wave periodic cortical inputs. Comparing models with and without FSIs reveals that the FSI network: (i) prevents the SPN network's generation of phase-locked beta oscillations in response to beta's harmonic frequencies, ensuring fidelity of transmission of cortical beta rhythms; and (ii) limits or entrains SPN activity in response to certain gamma frequency inputs. Chapter 3 describes an analysis of phase-amplitude coupling at cortical electrodes in human EEG data during a reward task. The alternating rhythms predicted by the model appear in response to positive feedback. While the origins of these rhythms remain unclear, if they represent striatal signals, they provide a direct link between human behavior and striatal cellular function.

No description available.