Zugl.: Berlin, Freie Universiẗat, Diss., 2008.

The dentate gyrus (DG) is a sub-region of the hippocampus which is important for memory formation and storage in the brain.  It comprises two major classes of neurons called granule cells (GCs), the local principal cells and the interneurons which receive sensory information from the entorhinal cortex (EC).  The GCs contain glutamate as neurotransmitter and excite the postsynaptic cells whereas the interneurons release GABA and inhibit the target cells.  While the GCs are abundant in number and transmit the processed information to CA3 via mossy fibres (MFs), the interneurons determine when and where the information flows through the principal cell network.  To understand how information is processed in DG, it is paramount to understand the role of interneurons in the network in detail.  Moreover, disruption of this basal transmission set-up forms the basis of many neurological disorders.  For example, reduced inhibition on GCs is implicated in epilepsy.  Treatment/prevention of such diseases also necessitates better understanding of the role of inhibition in DG. While greater degree of knowledge exists on how interneurons inhibit GCs, how they are activated by afferent inputs is not clear.  Hence, the present work is primarily focussed on studying the physiology behind synaptic activation of interneurons by afferent excitatory inputs in DG.  The results obtained might help in studying the causes of pathological conditions of DG in addition to elucidating the circuit mechanisms of information processing.

PURPOSE: To compare white matter neuron density across 3 regions, prefrontal, temporal, and posterior parietal (PFC, TE, PP) in macaque monkey, with further analysis of subdivisions within the gyral white matter. METHODS: Histological tissue from three adult macaque monkeys, previously prepared with the neuron-specific pan-neuronal marker Neuronal-N, was used for analysis. Tissue was digitized and processed electronically to investigate cross- and intra-regional differences in the distribution of white matter neurons. RESULTS: Statistical analysis showed significant differences across all regions sampled and across most intra-regional subdivisions, although the more conservative post-hoc tests failed to find significant differences between specific regions. CONCLUSIONS: The results of the current study support regional differences. Further studies using a larger sample size may help elucidate the relatively unknown properties of white matter neurons.

No description available.

New neurons are generated throughout adulthood in the dentate gyrus of the hippocampus. The aim of the current study was to address whether differences in the morphological complexity of adult-born granule cells affect their integration into existing dentate gyrus circuitry. To selectively label proliferating cells, we injected a CAG-retrovirus into the dentate gyrus of mice. Either 10, 20, 40, or 80 days following viral infection, mice were injected with pentylenetetrazol (PTZ) to induce hippocampal activation, and expression of the immediate early gene c-fos was used as a marker of activated neurons. We then compared morphological features of neurons across age groups and between Fos+ and Fos- neurons within each age group. We found that dendritic length and branch number increased from 10 to 20 days post infection. Unexpectedly, we also found that dendritic length and branch number decreased from 20 to 40 days post infection, suggesting that the maturation of adult-generated neurons is associated with an active pruning process. Furthermore, we found no significant difference in morphological complexity between Fos+ and Fos- neurons, suggesting that dendritic morphology does not influence integration into dentate gyrus circuitry.

New neurons are generated throughout adulthood in the dentate gyrus of the hippocampus. The aim of the current study was to address whether differences in the morphological complexity of adult-born granule cells affect their integration into existing dentate gyrus circuitry. To selectively label proliferating cells, we injected a CAG-retrovirus into the dentate gyrus of mice. Either 10, 20, 40, or 80 days following viral infection, mice were injected with pentylenetetrazol (PTZ) to induce hippocampal activation, and expression of the immediate early gene c-fos was used as a marker of activated neurons. We then compared morphological features of neurons across age groups and between Fos+ and Fos- neurons within each age group. We found that dendritic length and branch number increased from 10 to 20 days post infection. Unexpectedly, we also found that dendritic length and branch number decreased from 20 to 40 days post infection, suggesting that the maturation of adult-generated neurons is associated with an active pruning process. Furthermore, we found no significant difference in morphological complexity between Fos+ and Fos- neurons, suggesting that dendritic morphology does not influence integration into dentate gyrus circuitry.

No description available.

Psychiatric illnesses are disorders that affect millions worldwide. Evidence from quantitative and molecular genetics analysis suggests a strong genetic component to these disorders. There is also evidence that embryonic neurodevelopment is a key period in the progression schizophrenia. The aim of the present study was to use post-mortem human hippocampus from subjects of a variety of psychiatric phenotypes to investigate neurodevelopmentally- relevant gene expression in this region of the adult human brain. Particular interest is paid to schizophrenia risk gene DISC1; it has been shown to exhibit linkage and association to schizophrenia and is highly involved in embryonic and post natal neurodevelopmental processes. The results reported in this study indicate that DISC1 binding partners, and genes used to mark neurogenesis, can be found aberrantly expressed in schizophrenia and bipolar disorder, relative to controls. The results also suggest that DISC1 genotype may predict expression patterns of DISC1 binding partners and neurogenesis markers, irrespective of diagnosis. This may provide clues to the timing and nature of abnormal brain development in this illness and aid in development of treatment strategies.

Previous research has investigated intentional retrieval of contextual information and contextual influences on object identification and word recognition, yet few studies have systematically investigated context effects in episodic memory for objects. To address this issue, unique objects on a white background or embedded in a visually rich context were presented to participants. At test, the object was presented either in the original or a different context. Chapter 2 demonstrated that a context shift decrement (CSD)--decreased recognition performance when context is changed between encoding and retrieval--was observed. In four studies with young adults, the CSD was not attenuated by encoding or retrieval manipulations. Chapter 3 revealed that the CSD was resistant to aging and neuropsychological status. Importantly, older adults classified as high MTL performed better on the recognition task than those classified as low MTL, and as well as young adults, supporting the successful aging hypothesis. Chapter 4 focused on elucidating the neural correlates of the CSD using functional Magnetic Resonance Imaging. Right PHG activation during encoding was associated with subsequent recognition of objects in the context change condition. This same region was activated during recognition, suggesting it may automatically reinstate visual contextual information. Overall, the CSD is attributed to the automatic and obligatory binding of object and context information in episodic memory that results in an integrated representation, mediated by the hippocampal complex.

No description available.