Effects of alcohol on the generation and migration of cerebral cortical neurons

Prenatal exposure to alcohol produces many developmental defects of the central nervous system, such as microcephaly, mental retardation, motor dysfunction, and cognitive deficiencies. Therefore, the generation of neurons in the cerebral cortex was examined in the offspring of female rats fed a diet containing ethanol. Prenatal exposure to ethanol delayed and extended the period during which cortical neurons were generated, reduced the number of neurons in the nature cortex with the same time of origin, and altered the distribution of neurons generated on a particular day. Thus, the proliferation and migration of cortical neurons are profoundly affected by in utero exposure to ethanol.     

A map of visual space induced in primary auditory cortex

Maps of sensory surfaces are a fundamental feature of sensory cortical areas of the brain. The relative roles of afferents and targets in forming neocortical maps in higher mammals can be examined in ferrets in which retinal inputs are directed into the auditory pathway. In these animals, the primary auditory cortex contains a systematic representation of the retina (and of visual space) rather than a representation of the cochlea (and of sound frequency). A representation of a two-dimensional sensory epithelium, the retina, in cortex that normally represents a one-dimensional epithelium, the cochlea, suggests that the same cortical area can support different types of maps. Topography in the visual map arises both from thalamocortical projections that are characteristic of the auditory pathway and from patterns of retinal activity that provide the input to the map.     

Long-term potentiation in the motor cortex

Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills.     

Divided by cytochrome oxidase: a map of the projections from V1 to V2 in macaques

Current models partition the primate visual system into dorsal (magno) and ventral (parvo, konio) streams. Perhaps the strongest evidence for this idea has come from the pattern of projections between the primary visual area (V1) and the second visual area (V2). Prior studies describe three distinct pathways: magno to thick stripes, parvo to pale stripes, and konio to thin stripes. We now demonstrate that V1 output arises from just two sources: patch columns and interpatch columns. Patch columns project to thin stripes and interpatch columns project to pale and thick stripes. Projection of interpatches to common V2 stripe types (pale and thick) merges parvo and magno inputs, making it likely that these functional channels are distributed strongly to both dorsal and ventral streams.     

Patterning and plasticity of the cerebral cortex

The cerebral cortex of the human brain is a sheet of about 10 billion neurons divided into discrete subdivisions or areas that process particular aspects of sensation, movement, and cognition. Recent evidence has begun to transform our understanding of how cortical areas form, make specific connections with other brain regions, develop unique processing networks, and adapt to changes in inputs.     

Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations

In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (gamma-aminobutyric acid-releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain-specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior.     

Functional anatomy of the attentional modulation of time estimation

Attention modulates our subjective perception of time. The less we attend to an event's duration, the shorter it seems to last. Attention to time or color stimulus attributes was modulated parametrically in an event-related functional magnetic resonance imaging study. Linear increases in task performance were accompanied by corresponding increases in brain activity. Increasing attention to time selectively increased activity in a corticostriatal network, including pre-supplementary motor area and right frontal operculum. Increasing attention to color selectively increased activity in area V4. By identifying areas whose activity was specifically modulated by attention to time, we have defined the core neuroanatomical substrates of timing behavior.     

Auditory pathways to the frontal cortex of the mustache bat, Pteronotus parnellii

In primates, certain areas of the frontal cortex play a role in guiding movements toward visual or auditory objects in space. The projections from auditory centers to the frontal cortex of the bat Pteronotus parnellii were examined because echolocating bats utilize auditory cues to guide their movements in space. An area in the frontal cortex receives a direct projection from a division of the auditory thalamus, the suprageniculate nucleus, which in turn receives input from the anterolateral peri-olivary nucleus, an auditory center in the medulla. This pathway to the frontal cortex bypasses the main auditory centers in the midbrain and cortex and could involve as few as four neurons between the cochlea and the frontal cortex. The auditory cortex is also a major source of input to the frontal cortex. This area of the frontal cortex may link the auditory and motor systems by its projections to the superior colliculus.     

Cortex is driven by weak but synchronously active thalamocortical synapses

Sensory stimuli reach the brain via the thalamocortical projection, a group of axons thought to be among the most powerful in the neocortex. Surprisingly, these axons account for only approximately 15% of synapses onto cortical neurons. The thalamocortical pathway might thus achieve its effectiveness via high-efficacy thalamocortical synapses or via amplification within cortical layer 4. In rat somatosensory cortex, we measured in vivo the excitatory postsynaptic potential evoked by a single synaptic connection and found that thalamocortical synapses have low efficacy. Convergent inputs, however, are both numerous and synchronous, and intracortical amplification is not required. Our results suggest a mechanism of cortical activation by which thalamic input alone can drive cortex.     

Combinatorial effects of odorant mixes in olfactory cortex

In mammals, each odorant is detected by a combination of different odorant receptors. Signals from different types of receptors are segregated in the nose and the olfactory bulb, but appear to be combined in individual neurons in the olfactory cortex. Here, we report that binary odorant mixes stimulate cortical neurons that are not stimulated by their individual component odorants. We propose that cortical neurons require combinations of receptor inputs for activation and that merging the receptor codes of two odorants provides novel combinations of receptor inputs that stimulate neurons beyond those activated by the single odorants. These findings may explain why odorant mixtures can elicit novel odor percepts in humans.     

Ocular dominance column development: analysis and simulation

The visual cortex of many adult mammals has patches of cells that receive inputs driven by the right eye alternating with patches that receive inputs driven by the left eye. These ocular dominance patches (or "columns") form during early life as a consequence of competition between the activity patterns of the two eyes. A mathematical model of several biological mechanisms that can account for this development is presented. Analysis of this model reveals the conditions under which ocular dominance segregation will occur and determines the resulting patch width. Simulations of the model also exhibit other phenomena associated with early visual development, such as topographic refinement of cortical receptive fields, the confinement of input cell connections to patches, monocular deprivation plasticity including a critical period, and the effect of artificially induced strabismus. The model can be used to predict the results of proposed experiments and to discriminate among various mechanisms of plasticity.     

Computations underlying the execution of movement: a biological perspective

To execute voluntary movements, the central nervous system must transform the neural representation of the direction, amplitude, and velocity of the limb, represented by the activity of cortical and subcortical neurons, into signals that activate the muscles that move the limb. This task is equivalent to solving an "ill-posed" computational problem because the number of degrees of freedom of the musculoskeletal apparatus is much larger than that specified in the plan of action. Some of the mechanisms and circuitry underlying the transformation of motor plans into motor commands are described. A central feature of this transformation is a coarse map of limb postures in the premotor areas of the spinal cord. Vectorial combination of motor outputs among different areas of the spinal map may produce a large repertoire of motor behaviors.     

Subplate neurons pioneer the first axon pathway from the cerebral cortex

During the development of the nervous system, growing axons must traverse considerable distances to find their targets. In insects, this problem is solved in part by pioneer neurons, which lay down the first axonal pathways when distances are at a minimum. Here the existence of a similar kind of neuron in the developing mammalian telencephalon is described. These are the subplate cells, the first postmitotic neurons of the cerebral cortex. Axons from subplate neurons traverse the internal capsule and invade the thalamus early in fetal life, even before the neurons of cortical layers 5 and 6, which will form the adult subcortical projections, are generated. During postnatal life, after the adult pattern of axonal projections is firmly established, most subplate neurons disappear. These observations raise the possibility that the early axonal scaffold formed by subplate cells may prove essential for the establishment of permanent subcortical projections.     

Experimentally induced visual projections into auditory thalamus and cortex

Retinal cells have been induced to project into the medial geniculate nucleus, the principal auditory thalamic nucleus, in newborn ferrets by reduction of targets of retinal axons in one hemisphere and creation of alternative terminal space for these fibers in the auditory thalamus. Many cells in the medial geniculate nucleus are then visually driven, have large receptive fields, and receive input from retinal ganglion cells with small somata and slow conduction velocities. Visual cells with long conduction latencies and large contralateral receptive fields can also be recorded in primary auditory cortex. Some visual cells in auditory cortex are direction selective or have oriented receptive fields that resemble those of complex cells in primary visual cortex. Thus, functional visual projections can be routed into nonvisual structures in higher mammals, suggesting that the modality of a sensory thalamic nucleus or cortical area may be specified by its inputs during development.     

Convergent projection of three separate thalamic nuclei on to a single cortical area

Three distinct sensory-motor nuclei in the thalamus project to parietal cortex in the Virginia opossum; the ventral posterior nucleus receives inputs from somatic sensory structures and projects to layers IV and III, the ventral anterolateral nucleus receives inputs from motor structures and projects to layers IV and III and inner I, and the central intralaminar nucleus receives inputs from sensory, motor, and other structures and projects to layers VI through outer I. The physiologically defined amalgamation of somatic sensory and motor cortex is correlated, therefore, with the extent of cortex that receives convergent somatic sensory and motor input from the thalamus.     

Functional specialization in rhesus monkey auditory cortex

Neurons in the lateral belt areas of rhesus monkey auditory cortex prefer complex sounds to pure tones, but functional specializations of these multiple maps in the superior temporal region have not been determined. We tested the specificity of neurons in the lateral belt with species-specific communication calls presented at different azimuth positions. We found that neurons in the anterior belt are more selective for the type of call, whereas neurons in the caudal belt consistently show the greatest spatial selectivity. These results suggest that cortical processing of auditory spatial and pattern information is performed in specialized streams rather than one homogeneously distributed system.     

Descending efferents from the superior colliculus relay integrated multisensory information

By means of their efferent projections to motor and premotor structures, the cells in the deep superior colliculus are intimately involved in behaviors that control the orientation of the eyes, pinnae, and head. These same efferent cells receive multiple sensory inputs, thereby apparently enabling an animal to orient its receptor organs in response to a wide variety of cues. This sensory convergence also provides a system in which motor responses need not be immutably linked to individual stimuli but can vary in reaction to the multitude of stimuli present in the environment at any given moment.     

Bidirectional control of social hierarchy by synaptic efficacy in medial prefrontal cortex

Dominance hierarchy has a profound impact on animals' survival, health, and reproductive success, but its neural circuit mechanism is virtually unknown. We found that dominance ranking in mice is transitive, relatively stable, and highly correlates among multiple behavior measures. Recording from layer V pyramidal neurons of the medial prefrontal cortex (mPFC) showed higher strength of excitatory synaptic inputs in mice with higher ranking, as compared with their subordinate cage mates. Furthermore, molecular manipulations that resulted in an increase and decrease in the synaptic efficacy in dorsal mPFC neurons caused an upward and downward movement in the social rank, respectively. These results provide direct evidence for mPFC's involvement in social hierarchy and suggest that social rank is plastic and can be tuned by altering synaptic strength in mPFC pyramidal cells.     

Brain stem neurons in modified pathways for motor learning in the primate vestibulo-ocular reflex

The vestibulo-ocular reflex (VOR) stabilizes retinal images by generating smooth eye movements that are equal in amplitude and opposite in direction to head turns. Whenever image motion occurs persistently during head turns, the VOR undergoes motor learning; as a result image stability is gradually restored. A group of brain stem neurons that are in the modified pathways has now been described. The neurons express changes in firing in association with motor learning in the VOR and receive monosynaptic inhibition from the flocculus of the cerebellum. The changes in firing have an appropriate magnitude and are expressed at the correct latency to account for the altered VOR. The response properties of the neurons point to their brain stem vestibular inputs for further investigation of the site of motor learning.     

Reshaping the cortical motor map by unmasking latent intracortical connections

The primary motor cortex (MI) contains a map organized so that contralateral limb or facial movements are elicited by electrical stimulation within separate medial to lateral MI regions. Within hours of a peripheral nerve transection in adult rats, movements represented in neighboring MI areas are evoked from the cortical territory of the affected body part. One potential mechanism for reorganization is that adjacent cortical regions expand when preexisting lateral excitatory connections are unmasked by decreased intracortical inhibition. During pharmacological blockade of cortical inhibition in one part of the MI representation, movements of neighboring representations were evoked by stimulation in adjacent MI areas. These results suggest that intracortical connections form a substrate for reorganization of cortical maps and that inhibitory circuits are critically placed to maintain or readjust the form of cortical motor representations.