I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Interneurons of the hippocampus

The dentate granule cell layer of the rodent hippocampal formation has the distinctive property of ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and rodent models of limbic epilepsy, this same neuronal population undergoes extensive remodeling, including reorganization of mossy fibers, dispersion of the granule cell layer, and the appearance of granule cells in ectopic locations within the dentate gyrus. The mechanistic basis of these abnormalities, as well as their potential relationship to dentate granule cell neurogenesis, is unknown. We used a systemic chemoconvulsant model of temporal lobe epilepsy and bromodeoxyuridine (BrdU) labeling to investigate the effects of prolonged seizures on dentate granule cell neurogenesis in adult rats, and to examine the contribution of newly differentiated dentate granule cells to the network changes seen in this model. Pilocarpine-induced status epilepticus caused a dramatic and prolonged increase in cell proliferation in the dentate subgranular proliferative zone (SGZ), an area known to contain neuronal precursor cells. Colocalization of BrdU-immunolabeled cells with the neuron-specific markers turned on after division, 64 kDa, class III β-tubulin, or microtubule-associated protein-2 showed that the vast majority of these mitotically active cells differentiated into neurons in the granule cell layer. Newly generated dentate granule cells also appeared in ectopic locations in the hilus and inner molecular layer of the dentate gyrus. Furthermore, developing granule cells projected axons aberrantly to both the CA3 pyramidal cell region and the dentate inner molecular layer. Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration. These observations indicate that prolonged seizure discharges stimulate dentate granule cell neurogenesis, and that hippocampal network plasticity associated with epileptogenesis may arise from aberrant connections formed by newly born dentate granule cells.

https://www.jneurosci.org/content/jneuro/17/10/3727.full.pdf

Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus

Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity.

https://www.pnas.org/content/pnas/93/9/3908.full.pdf

Hippocampal atrophy in recurrent major depression

Early clinical observations and recent systematic studies overwhelmingly document a greater role for psychosocial stressors in association with the first episode of major affective disorder than with subsequent episodes. The author postulates that both sensitization to stressors and episode sensitization occur and become encoded at the level of gene expression. In particular, stressors and the biochemical concomitants of the episodes themselves can induce the protooncogene c-fos and related transcription factors, which then affect the expression of transmitters, receptors, and neuropeptides that alter responsivity in a long-lasting fashion. Thus, both stressors and episodes may leave residual traces and vulnerabilities to further occurrences of affective illness. These data and concepts suggest that the biochemical and anatomical substrates underlying the affective disorders evolve over time as a function of recurrences, as does pharmacological responsivity. This formulation highlights the critical importance of early intervention in the illness in order to prevent malignant transformation to rapid cycling, spontaneous episodes, and refractoriness to drug treatment.

Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.

Anatomy and pathology of the septal region.

Erratum: Progressive neuronal loss induced by kindling: A possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis (Brain Research, 527 (1990) 1-6)

Epileptic seizures are paroxysmal clinical events arising from neuronal hyperexcitability 
and hypersynchrony of the cerebral cortex, either locally or simultaneously in both 
hemispheres. A seizure occurs when there is a sudden imbalance between the excitatory 
and inhibitory inputs to a network of neurons such that there is overall excessive 
excitability. The behavioral manifestations of a seizure depend on the area of the cerebral 
cortex that is involved-directly, in the seizure focus, or indirectly, through recruitment 
and propagation of this abnormal paroxysmal neuronal activity. Convulsions are defined 
as seizures that include motor manifestations such as repeated and rhythmic jerking of the 
limbs, most often due to involvement of the motor cortex. Anticonvulsant drugs are 
medications that attempt to compensate for this abnormal cellular hyperexcitability by 
shifting the delicate balance back toward its normal state. Epilepsy is a chronic disorder 
characterized by recurrent unprovoked seizures, and is associated with a variety of 
medical conditions and neurological diseases. Antiepileptic medications attempt to treat 
this chronic seizure propensity, and, by definition, antiepileptogenic drugs aim to prevent 
the natural history of the epileptic disease.

Pathophysiology of Seizures and Epilepsy

Emerging data indicate that age-related brain changes alter seizure susceptibility, seizure-associated neurodegeneration, and responsiveness to AEDs The present study assessed long-term animal survival in the Kainic Acid (KA) model along with in-vivo spontaneous seizure frequency, cellular hyperexcitability in CA1 in-vitro and in-vivo in subiculum, and responsiveness of in-vitro CA1 hyperexcitability to topiramate Sprague-Dawley male rats were given KA to induce convulsive status epilepticus (KA-SE) at 2-3 months of age The one-month mortality after KA-SE was 27% One-month survivor rats had 37% sudden unexplained late mortality after KA-SE as compared to none in saline controls during their second year of life In-vivo seizure frequency was examined prior to terminal experiments The diurnal average seizure frequency in the KA-SE group at age 2 years was 106 ± 024 seizures/hour while no seizures were observed in the saline age-matched controls (p<0001) In-vitro recordings of CA1 pyramidal neurons revealed that depolarizing current injection from -60 mV evoked an increased number of action potentials in the aged KA-SE group compared to controls (p<0002) Topiramate exhibited dose-dependent inhibition of action potential firing evoked by current injections into CA1 pyramidal neurons of KA-SE rats In subiculum, KA-SE rats had frequent interictal spikes associated with high frequency oscillations while only rare spontaneous EPSPs were recorded in saline controls Our experiments revealed that the hippocampal formation of aged epileptic rats shares features of hyperexcitability previously described in young adult epileptic rats using the KA model

José E Cavazos

Papers

Anatomy and pathology of the septal region.

Erratum: Progressive neuronal loss induced by kindling: A possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis (Brain Research, 527 (1990) 1-6)

Pathophysiology of Seizures and Epilepsy

Chronic Cellular Hyperexcitability in Elderly Epileptic Rats with Spontaneous Seizures Induced by Kainic Acid Status Epilepticus while Young Adults.

Hippocampus: Normal magnetic resonance imaging anatomy with volumetric studies