Douglas O. Frost

Postnatal development of retinal projections in Syrian hamsters: a study using autoradiographic and anterograde degeneration techniques.

Abstract (1) In the Syrian hamster, there is a delay between the laying down of the trajectory of the optic tract (principally a prenatal event) and the formation by the optic tract of its various dense terminal projections (principally a postnatal event): At birth (Day 0), crossed retinofugal axons already cover the lateral geniculate body and extend into the superior colliculus. Although pioneering retinal efferents enter their target nuclei before Day 3, robust development of retinofugal axon telodendria is apparently delayed until that date; the onset of this arborization occurs simultaneously in the lateral geniculate body and superior colliculus, even though the axons of the optic tract pass over the lateral geniculate body before they arrive in the superior colliculus. (2) In all structures receiving binocular projections except the suprachiasmatic nucleus, the development of uncrossed optic tract axons lags behind the development of the crossed axons. (3) In regions where optic tract axons terminate in precise retinotopic order, the projections of the two eyes are segregated in adult animals, and the definitive patterns of connection develop gradually from less differentiated patterns: In the dorsal nucleus of the lateral geniculate body, crossed optic tract axons initially fill the entire nucleus, overlapping with the uncrossed axons; subsequently they withdraw from the ipsilateral projection zone, as the terminal distributions of uncrossed axons increase in density and volume. In adult hamsters, much of the uncrossed retinal input to the superior colliculus is distributed in multiple discrete clusters. Initially the clusters are not present, but develop gradually from a more diffuse pattern. (4) Since the adult distributions of crossed and uncrossed retinofugal projections are established before the time when the eyes open (Day 14), the factors which determine these distributions appear to be independent of exposure to patterned visual input. (5) In neonatal hamsters, as in adults, different populations of retinofugal axons may be distinguished by their differential rates of degeneration. (6) Some of the developmental changes in the hamsters retinal projections are similar to ontogenetic phenomena reported for other populations of central and peripheral axons.

Experience and the developing prefrontal cortex

The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.

Different programming modes of human saccadic eye movements as a function of stimulus eccentricity: Indications of a functional subdivision of the visual field

Abstract1. Voluntary saccadic eye movements were made toward flashes of light on the horizontal meridian, whose duration and distance from the point of fixation were varied; eye movements were measured using d.c.-electrooculography.—2. Targets within 10°–15° eccentricity are usually reached by one saccadic eye movement. When the eyes turn toward targets of more than 10°–15° eccentricity, the first saccadic eye movement falls short of the target by an angle usually not exceeding 10°. The presence of the image of the target off the fovea (visual error signal) subsequent to such an undershoot elicits, after a short interval, corrective saccades (usually one) which place the image of the target on the fovea. In the absence of a visual error signal, the probability of occurrence of corrective saccades is low, but it increases with greater target eccentricities. These observations suggest that there are different, eccentricity-dependent modes of programming saccadic eye movements.—3. Saccadic eye movements appear to be programmed in retinal coordinates. This conclusion is based on the observations that, irrespective of the initial position of the eyes in the orbit, a) there are different programming modes for eye movements to targets within and beyond 10°–15° from the fixation point, and b_ the maximum velocity of saccadic eye movements is always reached at 25° to 30° target eccentricity. —4. Distributions of latency and intersaccadic interval (ISI) are frequently multimodal, with a separation between modes of 30 to 40 msec. These observations suggest that saccadic eye movements are produced by mechanisms which, at a frequency of 30 Hz, process visual information. —5. Corrective saccades may occur after extremely short intervals (30 to 60 msec) regardless of whether or not a visual error signal is present; the eyes may not even come to a complete stop during these very short intersaccadic intervals. It is suggested that these corrective saccades are triggered by errors in the programming of the initial saccadic eye movements, and not by a visual error signal. —6. The exitence of different, eccentricity-dependent programming modes of saccadic eye movements, is further supported by anatomical, physiological, psychophysical, and neuropathological observations that suggest a dissociation of visual functions dependent on retinal eccentricity. Saccadic eye movements to targets more eccentric than 10°–15° appear to be executed by a mechanism involving the superior colliculus (perhaps independent of the visual cortex), whereas saccadic eye movements to less eccentric targets appear to depend on a mechanism involving the geniculo-cortical pathway (perhaps in collaboration with the superior colliculus).

The postnatal development of visual callosal connections in the absence of visual experience or of the eyes.

SummaryCounts of callosal neurons retrogradely labeled by horseradish peroxidase (visualized using multiple substrates) were obtained in areas 17 and 18 of five kittens reared with their eyelids bilaterally sutured and of three kittens which had undergone bilateral enucleation on postnatal days 1–4. These counts were compared with those obtained in normal adult cats.The normal adult distribution of the callosal neurons results from the gradual postnatal reduction of a more widespread juvenile population. Binocular visual deprivation by lid suturing dramatically decreases the final number of callosal neurons and narrows their region of distribution (callosal zone) in areas 17 and 18. A less severe reduction in the final number of callosal neurons is caused by bilateral enucleation, which also increases the width of the callosal zone compared to that of normal cats. Thus, visual experience is necessary for the normal stabilization of juvenile callosal connections. However, since some callosal neurons form connections in the absence of vision, other influences capable of stabilizing juvenile callosal neurons also exist. These influences are probably antagonized by destabilizing influences or inhibited, when the eyes are intact.

Anomalous visual connections to somatosensory and auditory systems following brain lesions in early life

When the principal sites of termination of retinofugal axons are removed in newborn hamsters and alternative terminal space is created by partial deafferentation of somatosensory or auditory thalamic nuclei, the optic axons form permanent ectopic connections in those nuclei. In operated hamsters, intraocularly injected radioactive label is transported transneuronally to the somatosensory or auditory cortices, suggesting that these higher order brain structures may process visual information.

Effects of methamphetamine-induced neurotoxicity on the development of neural circuitry: a hypothesis

Exposure of the developing brain to methamphetamine has well-studied biochemical and behavioral consequences. We review: (1) the effects of methamphetamine on mature serotonergic and dopaminergic pathways; (2) the mechanisms of methamphetamine neurotoxicity and (3) the role of serotonergic and dopaminergic signaling in sculpting developing neural circuitry. Consideration of these data suggest the types of neural circuit alterations that may result from exposure of the developing brain to methamphetamine and that may underlie functional defects.

Barrels in somatosensory cortex of normal and reeler mutant mice

The pattern of projection of the ventrobasal thalamic complex (VB) upon the neocortical barrel field of normal and reeler mutant mice was determined by orthograde degeneration experiments and by Timms histochemical method. In both reeler and normal mice the thalamic terminals are concentrated at the midcortical zone dominated by granule cells and the adjacent zone dominated by medium-sized pyramidal cells. The medium-sized pyramids are principally supragranular in normal cortex but infragranular in the reeler. Throughout the barrel fields of reeler and normal mice thalamic terminals are organized as a mosaic of radially oriented columns coextensive in the tangential plane with barrels whose cross-sectional areas and shapes are similar in both genotypes. The radial extent of the columns in reeler is 2-3 times that in normal cortex. These observations suggest that the tangential organization of the thalamocortical projection is normal in reeler and that thalamic terminals are distributed among the same neuronal classes in normal and reeler mice despite cell malposition in the mutant.

Early exposure to haloperidol or olanzapine induces long‐term alterations of dendritic form

Exposure of the developing brain to a wide variety of drugs of abuse (e.g., stimulants, opioids, ethanol, etc.) can induce life‐long changes in behavior and neural circuitry. However, the long‐term effects of exposure to therapeutic, psychotropic drugs have only recently begun to be appreciated. Antipsychotic drugs are little studied in this regard. Here, we quantitatively analyzed dendritic architecture in adult mice treated with paradigmatic typical‐ (haloperidol) or atypical (olanzapine) antipsychotic drugs at developmental stages corresponding to fetal or fetal plus early childhood stages in humans. In layer 3 pyramidal cells of the medial and orbital prefrontal cortices and the parietal cortex and in spiny neurons of the core of the nucleus accumbens, both drugs induced significant changes (predominantly reductions) in the amount and complexity of dendritic arbor and the density of dendritic spines. The drug‐induced plasticity of dendritic architecture suggests changes in patterns of neuronal connectivity in multiple brain regions that are likely to be functionally significant. Synapse 64: 191–199, 2010.

The fibroblast growth factor system is downregulated following social defeat

The fibroblast growth factor (FGF) system has previously been found to be altered in post-mortem brains of individuals with major depressive disorder (MDD). The present study tested whether the FGF system is altered following acute social defeat. Rats were exposed to four consecutive days of either a social defeat paradigm or novel cages. Animals were sacrificed after the last social defeat session and gene expression was assessed in the hippocampus by mRNA in situ hybridization. Molecular components of the FGF system were significantly downregulated following social defeat. Specifically, FGF2 and FGFR1 mRNA expression was decreased in various subfields of the hippocampus. Decreased tone of the FGF system following an acute social stressor is congruent with human post-mortem results of FGF system downregulation in depression. These findings suggest that modulating the FGF system may have therapeutic value in the treatment of MDD.

Chapter 28 When the auditory cortex turns visual

Abstract We studied visually guided behavior and the visual response properties of single auditory cortex (A1) neurons in neonatally operated hamsters with surgically induced, permanent, ectopic retinal projections to auditory thalamic nuclei and to visual thalamic nuclei which normally receive little direct retinal input. The surgically induced retino-thalamo-cortical pathways can mediate visual guided behaviors whose normal substrate, the pathway from the retina to the primary visual cortex via the primary thalamic visual nucleus, is missing. The visually evoked response properties of A1 neurons resemble in many respects those of neurons in V1 of normal hamsters: many A1 neurons have well-defined visual reseptive fields and preferences for orientation or direction of movement. In addition, some visually responsive cells in A1 are bimodal — they also respond to auditory stimuli. The visually responsive neurons in A1 probably account for the capacity of the auditory cortex to mediate visual behavior in ‘rewired hamsters’.