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Plasticity of synapses is not static across the lifespan. As the brain matures and ages, the ability of neurons to undergo structural and functional change becomes more limited. Further, there are a number of modulatory factors that influence the expression of synaptic plasticity. Here, three approaches were taken to examine and manipulate plasticity in the auditory thalamocortical system of rats. Using an in vivo preparation, long-term potentiation (LTP) and paired pulse (PP) responses were used as measures of long- and short-term plasticity, respectively. First, the effect of intracortical zinc application in the primary auditory cortex (A1) on LTP was examined. Following theta burst stimulation (TBS) of the medial geniculate nucleus (MGN), juvenile and middle-age rats, but not young adults, showed greater levels of LTP with zinc application relative to age-matched control animals. Next, PP responses were examined between rats reared in unaltered acoustic conditions and those reared in continuous white noise (WN) from postnatal day (PD) 5 to PD 50-60 (i.e., subjected to patterned sound deprivation). Rats reared in WN demonstrated less PP depression relative to controls, indicating that WN rearing alters short-term thalamocortical synaptic responses. Furthermore, control males showed no change in PP response following LTP induction, indicating a postsynaptic locus of LTP, whereas increased PP depression following LTP induction was seen in WN animals, suggestive of a presynaptic involvement in LTP. Finally, differences in plasticity between male and female rats were investigated, and the result of early WN exposure on both sexes was examined. Males and females did not show consistent differences in LTP expression; however WN exposure appeared to affect LTP of females less than their male counterparts. PP responses were then compared between WN-reared males and females, and no difference was found. This indicates that short-term plastic properties of auditory thalamocortical synapses between the sexes do not differ, even though plasticity on a longer time scale following sensory deprivation does indicate some difference. Together, the experiments summarized here identify some of the important factors that contribute to the regulation of short- and long-term synaptic plasticity in the central auditory system of the mammalian brain. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2012-10-30 16:01:28.796

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This thesis aimed to investigate the role of the perirhinal cortex in object memory in the rat. The first experiment tested the hypothesis that the perirhinal cortex is critical to memory for relationships between objects by testing postoperative learning of novel visual-visual stimulus associations following lesions of the perirhinal cortex. The hypothesis was not supported: postoperative performance was not impaired. Experiments 3.1-3.4 tested the hypothesis that perirhinal cortex is crucial to the integration of multiple features into a representation of an object using spontaneous object recognition with either reconfigured objects or multiple objects. The hypothesis was supported: perirhinal lesions caused disproportionate impairment on tasks involving feature ambiguity. Experiments 4.1-4.7 investigated the effects of, perirhinal, postrhinal or fornix lesions on aspects of memory for object-context associations. The hypothesis that postrhinal and fornix lesioned animals would be more impaired than perirhinal animals was confirmed. Postrhinal lesions impaired memory for object-context associations, as, less severely, did fornix lesions; perirhinal lesions impaired memory when another object was used as the context. Experiment 5.1 used a novel model for episodic-like memory and tested the hypothesis that postrhinal or fornix, but not perirhinal lesions would cause impairment. One of these predictions was supported: fornix but not postrhinal or perirhinal lesions caused severe impairment of episodic-like memory. The fornix impairment was not due to an impairment of memory for object-place associations (experiment 5.2). Finally, experiments 6.1-6.7 investigated the possible function of L-type calcium channels in perirhinal cortex. The dihydropyridine nimodipine was successfully used to reverse the effects of the muscarinic antagonist scopolamine on the spontaneous object recognition task. It is concluded that perirhinal lesions in the rat result in impairments of memory which involve the processing of objects and the relation of their constituent features to each other. They do not impair memory for the association either of distinct objects or of objects and background contexts or locations. This is contrasted with the impairment of memory for object-in-context which results from postrhinal lesions and the impairment of episodic- like memory which results from fornix lesions. The importance of the cholinergic system in object recognition is confirmed and the importance of L-type calcium channels to such memory is suggested.

A Dissertation Submitted to the Faculty oC Arts University of the Witwatersrand, Johannesburg for the Degree of Master of Arts Johannesburg, 1974 / The relationship between amygdaloid damage and the intmperitoneal injection of betamethasone was studied with respect to the exploratory behaviour of male hooded rats. Amygdalaetomy produced attenuated longterm habituation of stimulus-specific and general exploratory behaviour. This habituation deficit was uninfluenced by betamethasone. Betamethasone also failed to influence long-tori. habituation in the intact animals. Although amygdalectomy did not alter short-term habituation, betamethasone accelerated the short-term habituation of general exploratory behaviour in both amygdalectomised and intact animals. On replication of the experiment betamethasone administration failed to influence exploration. It was tentatively concluded that amygdalectomy and betamethasone influence the habituation of exploratory activity under mutually exclusive circumstances. However, the failure to replicate the amygdalectomy- and betamethasone- induced changes in habituation could not be inteipreted within the context of the present experiment.

D. Phil., School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 2011 / Whether the neuropil is a static, optimally wired entity, whose components must be balanced in a certain way, is an open question. Are the proportions of the components of the neuropil consistent across different mammalian cortices, especially in primates where the cerebral cortex is complexly organized? This question is interesting because the actual biological underpinnings of complex behaviours and intelligence in big-brained primates remain enigmatic and why they seem qualitatively different from other animals in terms of their cognitive abilities. Understanding changes that may have occurred in the brain, especially at the level of neuropil organization, during the evolution in primates is important to our growing understanding of the intellectual abilities and behaviours exhibited by members of this group. The current series of quantitative studies was aimed at investigating variations in the proportionality of the “wire fraction” in three primate species, the olive baboon (Papio anubis), vervet monkey (Cercopithecus aethiops) and the common chimpanzee (Pan troglodytes), in a range of higher and lower order cortical areas, using a newly developed method that involves standard and immunohistochemical staining techniques to reveal and quantify the various profiles of the fine structures of the cerebral cortex. The results of these studies demonstrate clear layer differences in the wire fraction of the cerebral cortex, and for the most part, consistency in the neuropil wire fraction of the same layer across areas of the cerebral cortex within and between individuals of the same species; however, differences in the wire fraction of the neuropil were associated with changes in brain size. It is apparent that the neuropil is not static, as wiring “optimality” changes with layers and brain size and this has functional implications regarding neuronal processing and behavioural outcomes. The adaptive rationale adopted by evolutionary psychology studies to explain behaviours may be erroneous, as adaptation does not always explain sufficiently the emergence of complex behaviours related to brain size increases, especially in primates.

Sensory information is represented in cortex by cascades of excitation, the patterns of which are constrained and biased by anatomical connections between neurons. Additionally, in the living animal, functional connectivity is dynamically adjusted by internally generated background activity, which varies by arousal state and behavioral context. Therefore, to understand how excitation propagates through the cortex, it is necessary to characterize the laminar flow of signal propagation as well as spontaneous network activity, which will constrain that propagation. This thesis characterizes the nature and mechanisms of awake cortical network dynamics, as well as the sources of sensory inputs in different cortical layers of the rat somatosensory system. Mammalian brains generate internal activity independent of environmental stimuli. Internally generated states may bring about distinct cortical processing modes. To investigate how brain state impacts cortical circuitry, we recorded intracellularly from the same neurons, under anesthesia and subsequent wakefulness, in the rat barrel cortex. In every cell examined throughout layers 2-6, wakefulness produced a temporal pattern of synaptic inputs differing markedly from those under anesthesia. Recurring periods of synaptic quiescence, prominent under anesthesia, were abolished by wakefulness, which produced instead a persistently depolarized state. This switch in dynamics was unaffected by elimination of afferent synaptic input from thalamus, suggesting that arousal alters cortical dynamics by neuromodulators acting directly on cortex. Indeed, blockade of noradrenergic, but not cholinergic, pathways induced synaptic quiescence during wakefulness. This thesis shows that subcortical inputs from the locus coeruleus-noradrenergic system can switch local recurrent networks into different regimes via direct neuromodulation. Having characterized the nature of wakeful dynamics, I next sought to characterize how sensory information propagates through the cortex. The thalamocortical projection to layer 4 (L4) of primary sensory cortex is thought to be the main route by which information from sensory organs reaches the neocortex. Sensory information is believed to then propagate through the cortical column along the L4→L2/3→L5/6 pathway. This thesis shows that sensory-evoked responses of L5/6 neurons derive from direct thalamocortical synapses, rather than the intracortical pathway. A substantial proportion of L5/6 neurons exhibit sensory-evoked postsynaptic potentials and spikes with the same latencies as L4. Paired in vivo recordings from L5/6 neurons and thalamic neurons revealed significant convergence of direct thalamocortical synapses onto diverse types of infragranular neurons. Pharmacological inactivation of L4 had no effect on sensory-evoked synaptic input to L5/6 neurons, and responsive L5/6 neurons continued to discharge spikes. In contrast, inactivation of thalamus suppressed sensory-evoked responses. This thesis shows that L4 is not an obligatory distribution hub for cortical activity, contrary to long-standing belief, and that thalamus activates two separate, independent "strata" of cortex in parallel.

Of all sensory cortical areas, barrel cortex is among the best understood in terms of circuitry, yet least understood in terms of sensory function. Because sensory cortical areas have stereotyped anatomies, understanding computations in one sensory area may inform us of computations being performed by other sensory areas or sensory microcircuits all over the brain. Functional studies of barrel cortex are therefore important for marrying our immense and increasing knowledge of the cortical circuitry with the computations being performed in a cortical microcircuit. This thesis is an investigation of barrel cortex function as it pertains to 1) site specific sensory evoked plasticity in cortical microcircuit and 2) sensory receptive fields of the different cortical lamina in S1. The brain's capacity to rewire is thought to diminish with age. It is widely believed that development stabilizes the synapses from thalamus to cortex and that adult experience alters only synaptic connections between cortical neurons. We combined whole-cell recording from individual thalamocortical neurons in adult rats with a newly developed automatic tracing technique to reconstruct individual axonal trees. Whisker trimming substantially reduced thalamocortical axon length in barrel cortex but not the density of TC synapses along a fiber. Thus, sensory experience alters the total number of TC synapses. After trimming, sensory stimulation evoked more tightly time-locked responses among thalamorecipient layer 4 cortical neurons. Axonal plasticity was topographically specific, with robust changes in L4 and modest changes in the septal and infragranular layers. These results indicate that plasticity is mediated by interactions with the local cortical subcircuit and may be suggestive of laminar specific roles in sensory learning/coding. Next we sought to examine spatiotemporal coding properties of neurons in the different layers of the cortical microcircuit in S1. We combined intracellular recording and a novel multi-directional multi-whisker stimulator system to estimate receptive fields by reverse correlation of stimuli to synaptic inputs. Spatiotemporal receptive fields were identified orders of magnitude faster than by conventional spike-based approaches, even for neurons with little or no spiking activity. Given a suitable stimulus representation, a simple linear model captured the stimulus-response relationship for all neurons with unprecedented accuracy. In contrast to conventional single-whisker stimuli, complex stimuli revealed dramatically sharpened receptive fields, largely due to the effects of adaptation. Surprisingly, this phenomenon allows the surround to facilitate rather than suppress responses to the principal whisker. Optimized stimuli enhanced firing in layers 4-6, but not 2/3, which remained sparsely active. Surround facilitation through adaptation may be required for discriminating complex shapes and textures during natural sensing.