Mechanisms of Information Processing in the Chick

The kinetics of neurobiological phenomena involved in 1he formation of a memory trace were examined in the first two experiments. Transcranial subconvulsive current was administered to large groups of chicks at various intervals following an aversive training experience. The resulting retrograde amnesia data indicate that immediately upon training a metastable mnemonic process becomes activated (STM) which then remains at a constant intensity. Within a minute STM induces a more permanent form of memory (Pre-LTM) to grow at a steadily declining rate, apparently as some restricted neural substrate of memory becomes exhausted. STM may continue to function as behaviorally accessible memory for the next few hours, during which time the behaviorally latent Pre-LTM trace undergoes a subsequent transition into permanent memory. An investigation of the retrograde amnesia resulting from a sequence of two training-current sessions provides support to the existence of these mechanisms and indicates that fractional engrams summate together in a simple fashion. To examine the participation of different cerebral structures in information processing, chicks having various telencephalic lesions were tested in either a passive avoidance task or an appetitive discrimination. The hippocampus was found to be involved in reversal but not acquisition of the pattern discrimination, and in acquisition but not retrieval of the passive avoidance task. On the other hand, the amygdala seems to be important both for retrieval and acquisition of passive avoidance conditioning, but only for early stages of acquiring the pattern discrimination. Frontal ablations resulted in a deficit to retrieval but not to acquisition of passive avoidance conditioning, and caused some motivational changes independent of chicks' learning ability in the performance of the appetitive task. A comparison of these results with those following lesions in homologous mammalian limbic system structures suggests that the information processing of both classes is based upon cerebral mechanisms which have remained unchanged despite their divergent evolution. Mechanisms of memory processing and interhemispheric transfer were further studied in chicks having extensive unilateral ablations of the dorsal telencephalon, a region critical for visual learning. Although chicks were able to acquire a passive avoidance response equally well using either the eye ipsilateral or that contralateral to the surgery, subsequent extinction conditioning could be learned only through the ipsilateral eye. Since retinal projections cross completely at birds' optic chiasma, these results suggest that anatomically distinct systems, one bilaterally represented, the other lateralized, respectively mediate the acquisition and extinction of the aversive response. An inability or lateralized memory to transfer through the commissures is indicated by the absence of interocular transfer for monocularly learned extinction.</p

Inosine Enhances Axon Sprouting and Motor Recovery after Spinal Cord Injury

Although corticospinal tract axons cannot regenerate long distances after spinal cord injury, they are able to sprout collateral branches rostral to an injury site that can help form compensatory circuits in cases of incomplete lesions. We show here that inosine enhances the formation of compensatory circuits after a dorsal hemisection of the thoracic spinal cord in mature rats and improves coordinated limb use. Inosine is a naturally occurring metabolite of adenosine that crosses the cell membrane and, in neurons, activates Mst3b, a protein kinase that is part of a signal transduction pathway that regulates axon outgrowth. Compared to saline-treated controls, rats with dorsal hemisections that were treated with inosine showed three times as many synaptic contacts between corticospinal tract collaterals and long propriospinal interneurons that project from the cervical cord to the lumbar level. Inosine-treated rats also showed stronger serotonergic reinnervation of the lumbar cord than saline-treated controls, and performed well above controls in both open-field testing and a horizontal ladder rung-walking test. Inosine was equally effective whether delivered intracranially or intravenously, and has been shown to be safe for other indications in humans. Thus, inosine might be a useful therapeutic for improving outcome after spinal cord injury

Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Injury: Role of Inflammation and Other Factors

The optic nerve, like most pathways in the mature central nervous system, cannot regenerate if injured, and within days, retinal ganglion cells (RGCs), the neurons that extend axons through the optic nerve, begin to die. Thus, there are few clinical options to improve vision after traumatic or ischemic optic nerve injury or in neurodegenerative diseases such as glaucoma, dominant optic neuropathy, or optic pathway gliomas. Research over the past two decades has identified several strategies to enable RGCs to regenerate axons the entire length of the optic nerve, in some cases leading to modest reinnervation of di- and mesencephalic visual relay centers. This review primarily focuses on the role of the innate immune system in improving RGC survival and axon regeneration, and its synergy with manipulations of signal transduction pathways, transcription factors, and cell-extrinsic suppressors of axon growth. Research in this field provides hope that clinically effective strategies to improve vision in patients with currently untreatable losses could become a reality in 5–10 years

The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects

The 4.2-kilodalton (kDa) polypeptide associated with the cerebral amyloid deposits of Alzheimer\u27s disease (AD) derives from a much larger protein that is encoded by a gene on chromosome 21. In the present study, we have used antibodies raised against portions of the amyloid protein precursor (APP) to map its normal distribution and to gain further insights into the events that lead to amyloid deposition. Antibodies raised againt several different portions of APP reacted with proteins having apparent molecular sizes of 65, 67, and 132 kDa on Western blots. In sections through the normal human brain, immunocytochemistry revealed punctate concentrations of the protein in pyramidal cells of the neocortex, particularly in associative regions, and intense staining in the CA1 pyramidal cells of the hippocampus. By electron microscopy, this punctate distribution coincided with dense concentrations of the protein in secondary lysosomes. In the hippocampus of several AD cases examined, abnormally dense immunostaining in enlarged intracellular domains accompanied a severe atrophy of the CA1 neurons. These data suggest that accumulations of APP in lysosomes of particular neurons may, in AD, lead to proteolytic events that form the insoluble 4.2-kDa amyloid peptide. © 1989