Spatial distribution of inhibitory synaptic connections during development of ferret primary visual cortex

Intracortical inhibition in the primary visual cortex plays an important role in creating properties like orientation and direction selectivity. However, the development of the spatial pattern of inhibitory connections is largely unexplored. This was investigated in the present study. Tangential slices of layers 2/3 of ferret striate cortex were prepared for whole-cell patch clamp recordings, and presynaptic inhibitory inputs to pyramidal neurons were scanned by local photolysis of Nmoc-caged glutamate. Inhibitory synaptic currents (IPSCs) were first detected around postnatal day (P) 17. They originated locally around the recorded cells. Both the number and the total areas supplying the inhibitory inputs increased thereafter and peaked at the time around and shortly after eye opening (P29–37). A refinement period then followed in which the areas providing the majority of inhibitory inputs shrank from 600 µm around the recorded neurons to 200–300 µm in more mature animals (P38). The amplitude of IPSCs increased progressively with increasing age. Long-range inhibitory inputs (>600 µm) were present around eye opening and they often developed into a clustered patchy pattern in more mature animals (P38). In summary, our results show a refinement and clustering in the spatial pattern of inhibitory connections during postnatal development of ferret visual cortex.     

Laminar sources of synaptic input to cortical inhibitory interneurons and pyramidal neurons

The functional role of an individual neuron within a cortical circuit is largely determined by that neuron's synaptic input. We examined the laminar sources of local input to subtypes of cortical neurons in layer 2/3 of rat visual cortex using laser scanning photostimulation. We identified three distinct laminar patterns of excitatory input that correspond to physiological and morphological subtypes of neurons. Fast-spiking inhibitory basket cells and excitatory pyramidal neurons received strong excitatory input from middle cortical layers. In contrast, adapting inhibitory interneurons received their strongest excitatory input either from deep layers or laterally from within layer 2/3. Thus, differential laminar sources of excitatory inputs contribute to the functional diversity of cortical inhibitory interneurons.     

Perinatal subplate neuron injury: implications for cortical development and plasticity

Perinatal brain injury may result in widespread deficits in visual, motor and cognitive systems suggesting disrupted brain development. Neurosensory and cognitive impairment are observed at increasing frequency with decreasing gestational ages, suggesting a unique vulnerability of the developing brain. The peak of human subplate neuron development coincides with the gestational ages of highest vulnerability to perinatal brain injury in the premature infant. At the same time, human thalamocortical connections are forming and being refined by activity-dependent mechanisms during critical periods. Subplate neurons are the first cortical neurons to mature and are selectively vulnerable to early hypoxic-ischemic brain injury in animal models. Timing of subplate neuron death determines the resulting defect in thalamocortical development: very early excitotoxic subplate neuron death results in failure of thalamocortical innervation, while later subplate neuron death interferes with the refinement of thalamocortical connections into mature circuits. We suggest that subplate neuron injury may be a central component of perinatal brain injury resulting in specific neurodevelopmental consequences.     

In vitro approach to visual cortical development and plasticity.

The neural circuitry in the visual cortex is characterized by two basic types of organization. One is a laminar organization determining the extrinsic and intrinsic neural connections of cortical cells according to their cortical depth, and the other is a columnar organization where cortical cells are arranged perpendicularly according to their response selectivities. It is known that the columnar organization comprises the postnatal structures dependent on the visual experience, while the laminar organization comprises the prenatal structures unmodified by visual experience. We have investigated the interplay between the pre- and postnatal mechanisms using various in vitro preparations, including visual cortical slices, and transplant and co-culture preparations. It was shown in lateral geniculate and visual cortex transplants and co-cultures including the visual cortex lateral geniculate nucleus that all laminar structures are expressed in these preparations according to the prenatal mechanisms. It was also shown in slice preparations that the details of these circuitries are plastic and modifiable by the visual input, although their basic framework is determined prenatally.     

Topographical and laminar distribution of cortical input to the monkey entorhinal cortex

Hippocampal formation plays a prominent role in episodic memory formation and consolidation. It is likely that episodic memory representations are constructed from cortical information that is mostly funnelled through the entorhinal cortex to the hippocampus. The entorhinal cortex returns processed information to the neocortex. Retrograde tracing studies have shown that neocortical afferents to the entorhinal cortex originate almost exclusively in polymodal association cortical areas. However, the use of retrograde studies does not address the question of the laminar and topographical distribution of cortical projections within the entorhinal cortex. We examined material from 60 Macaca fascicularis monkeys in which cortical deposits of either (3)H-amino acids or biotinylated dextran-amine as anterograde tracers were made into different cortical areas (the frontal, cingulate, temporal and parietal cortices). The various cortical inputs to the entorhinal cortex present a heterogeneous topographical distribution. Some projections terminate throughout the entorhinal cortex (afferents from medial area 13 and posterior parahippocampal cortex), while others have more limited termination, with emphasis either rostrally (lateral orbitofrontal cortex, agranular insular cortex, anterior cingulate cortex, perirhinal cortex, unimodal visual association cortex), intermediate (upper bank of the superior temporal sulcus, unimodal auditory association cortex) or caudally (parietal and retrosplenial cortices). Many of these inputs overlap, particularly within the rostrolateral portion of the entorhinal cortex. Some projections were directed mainly to superficial layers (I-III) while others were heavier to deep layers (V-VI) although areas of dense projections typically spanned all layers. A primary report will provide a detailed analysis of the regional and laminar organization of these projections. Here we provide a general overview of these projections in relation to the known neuroanatomy of the entorhinal cortex.     

Abnormal patterns of cortical synaptic connectivity in schizophrenia

Electron microscopic morphometric study of postmortem prefrontal cortex (area 10) and visual cortex (area 17) was performed to estimate the numeric density (Nv) of synapses in layers I and II, neurons in layer II and the number of synapses per neuron in layer II in 20 cases of chronic schizophrenia and 16 healthy controls using stereological physical dissector method. In the prefrontal cortex the Nv of axospinous synapses was significantly lower in layer I (-20%, p < 0.05) in schizophrenia group and in the subgroup with predominantly positive symptoms as compared to controls (p < 0.05). On the contrary, a significantly higher Nv of synapses (+24%, p < 0.05) and the number of synapses per neuron were found in layer II (+42%, p < 0.05) in schizophrenia group and in the subgroups of cases with predominantly negative symptoms and a continuous course of schizophrenia (p < 0.001) as compared to the control group. The subgroup of cases with predominantly negative symptoms displayed a significantly lower number of neurons in layer II of the prefrontal cortex compared to controls (p < 0.05) and the subgroup of cases with predominantly positive symptoms (p < 0.01). In the visual cortex the number of axodendritic synapses per neuron in layer II was significantly higher in schizophrenia, but the other parameters did not differ from those in the control group. These prominent abnormalities of synaptic connectivity might be the structural basis for altered cognitive functions associated with changes in intracortical, cortico-cortical, and cortico-subcortical pathways, and could contribute to the formation of positive and negative symptoms and altered neuronal plasticity in patients with schizophrenia.     

Changing patterns of binocular visual connections in the intertectal system during development of the frog,Xenopus laevis

During metamorphic and post-metamorphic life in the frog. Xenopus laevis, growth-related changes in skull shape produce radical alterations in the spatial relationship between the two eyes. These changes in binocular visual geometry were measured using optical techniques. Between the onset of metamorphic climax at stage 60 and adulthood (2 or more years post-metamorphosis) each eye migrates nasally by 55 degrees and dorsally by 50 degrees with respect to the major body axes of the animal. As a result the nasotemporal extent of the binocular visual field increases from 30 degrees to 162 degrees between these ages. Electrophysiological methods were used to determine changes in the neural representation of the binocular visual field at the paired midbrain optic tecta and in the tectal projection of pairs of corresponding retinal loci at various developmental points between these ages. The proportion of each tectal surface devoted to the representation of the binocular visual field increases from 11% at stage 60 to 77% at adulthood. Retinal correspondence, and hence the tectal projection of corresponding retinal loci, undergoes radical alteration during this period. In normal adults an intertectal system of connections selectively links the tectal projection of corresponding retinal loci and thus provides a neuronal mechanism for integrating binocular visual information in the optic tecta. Electrophysiological methods were used to determine how the intertectal system accommodates the developmental challenge posed by the enlarging binocular visual field and changing retinal correspondence. Between stage 60 and adulthood the ipsilateral visuotectal projection which is the product of the intertectal system, increases in size as the binocular visual field and its tectal representation enlarges. Moreover, throughout this period, it provides a mechanism for integrating binocular visual information in the optic tecta by maintaining its spatial registration with the contralateral visuotectal projection from the other eye. Analysis of the pattern of functional intertectal connections reveals that during the course of normal maturation this system undergoes continuous processes of expansion and of orderly and major remodelling.     

Changing patterns of binocular visual connections in the intertectal system during development of the frog,Xenopus laevis

Summary In the frog, Xenopus laevis, a system of intertectal connections underlies the visual projection from an eye to its ipsilateral tectal lobe and is involved in the topographic representation of binocular visual space. Rotation of one eye in early life may be followed by a radical rearrangement of the connections in this system. The modified pattern which later emerges is that which keeps the visual projection through the ipsilateral eye in topographic registration with the direct visual projection from the contralateral eye to the same tectal lobe. This plasticity requires visual experience.In this paper we describe the time-course and sequence of events by which this plasticity is effected. Following rotation of one eye in larval animals or in animals undergoing metamorphic climax, the earliest evidence of intertectal modification was found 3–4 weeks after metamorphosis. With increasing intervals after metamorphosis an increasing proportion of animals displayed modified intertectal systems. At intermediate intervals many animals showed partial modifications, which were interpreted as transitional stages in the modification process. Analysis of these transitional stages indicated that the sequence of events involved in the elaboration of a modified intertectal system following the experimental alteration of eye alignment exhibits features in common with rearrangements of the system that occur during normal development in response to growth-related alterations in eye alignment.     

Changing patterns of binocular visual connections in the intertectal system during development of the frog,Xenopus laevis

Summary During normal metamorphic and postmetamorphic growth of the frog, Xenopus laevis, there is a major and orderly remodelling of the pattern of neuronal connections in the intertectal system. These changes preserve the spatial registration of binocular visual inputs to each optic tectum in the face of continuous changes in relative eye alignment (Grant and Keating 1989). We suggested that visual experience might be utilised by the intertectal system to effect the maturational remodelling of its connections, with particular involvement in maintaining binocular visual registration. To investigate this suggestion we studied the development of the intertectal system in animals that had been reared in total darkness from before the onset of function in the system. Visual deprivation did not affect the developmental ocular migration that normally occurs in Xenopus, nor did it affect the maturation of the contralateral visuotectal projection. Abnormalities were, however, observed in the ipsilateral visuotectal projection of all dark-reared animals studied, reflecting perturbation of the underlying intertectal system. The abnormalities included disorder and deficits in the projection, which became more marked with age. Quantitative analyses of the spatial registration of binocular visual inputs to the optic tectum revealed that, in all dark-reared animals studied, registration was both significantly poorer and systematically shifted compared to normal controls. Analysis of maturational changes in the pattern of intertectal connections in visually-deprived animals led to the conclusion that intrinsic developmental processes generate an initially well-organised intertectal system and programme much of its continuous expansion with age. Visual experience, however, is necessary for the large scale and orderly remodelling of the system which, during normal maturation, preserves binocular visual registration despite changes in interocular alignment.     

Subcortical auditory input to the primary visual cortex in anophthalmic mice

Anatomical and imaging studies show ample evidence for auditory activation of the visual cortex following early onset of blindness in both humans and animal models. Anatomical studies in animal models of early blindness clearly show intermodal pathways through which auditory information can reach the primary visual cortex. There is clear evidence for intermodal corticocortical pathways linking auditory and visual cortex and also novel connections between the inferior colliculus and the visual thalamus. A recent publication [L.K. Laemle, N.L. Strominger, D.O. Carpenter, Cross-modal innervation of primary visual cortex by auditory fibers in congenitally anophthalmic mice, Neurosci. Lett. 396 (2006) 108–112] suggested the presence of a direct reciprocal connection between the inferior colliculus and the primary visual cortex (V1) in congenitally anophthalmic ZRDCT/An mice. This implies that this mutant mouse would be the only known vertebrate having a direct tectal connection with a primary sensory cortex. The presence of this peculiar pathway was reinvestigated in the ZRDCT/An mouse with highly sensitive neuronal tracers. We found the connections normally described in the ZRDCT/An mouse between: (i) the inferior colliculus and the dorsal lateral geniculate nucleus, (ii) V1 and the superior colliculus, (iii) the lateral posterior nucleus and V1 and between (iv) the inferior colliculus and the medial geniculate nucleus. We also show unambiguously that the auditory subcortical structures do not connect the primary visual cortex in the anophthalmic mouse. In particular, we find no evidence of a direct projection from the auditory mesencephalon to the cortex in this animal model of blindness.     

Specificity and non-specificity of synaptic connections within mammalian visual cortex

It is clear from reviewing the findings of our own studies and those of others that the cerebral cortex has combined two very different strategies of organisation. Firstly it has a strictly defined genetically determined substrate of specific neurons classes, specific rules for which kinds of cells interconnect, a laminar architecture where efferent and afferent relays and interlaminar links are predetermined. But, as well, a second strategy allows great developmental lability in the precise spatial patterns of intralaminar circuits of the excitatory neurons and in the actual weights of excitatory and inhibitory synapses that are contributed to each neuron. This second strategy presumably allows the cortex to be tailor-made to the early experience of each individual and, as well, allow for lability of responses to different conditions of stimulation and adjustment of the system to compensate to some degree for injuries affecting afferents and circuitry in the adult system.     

Effect of stochastic synaptic and dendritic dynamics on synaptic plasticity in visual cortex and hippocampus

Various forms of synaptic plasticity, including spike timing-dependent plasticity, can be accounted for by calcium-dependent models of synaptic plasticity. However, recent results in which synaptic plasticity is induced by multi-spike protocols cannot simply be accounted for by linear superposition of plasticity due to spike pairs or by existing calcium-dependent models. In this paper, we show that multi-spike protocols can be accounted for if, in addition to the dynamics of back-propagating action potentials, stochastic synaptic dynamics are taken into account. We show that a stochastic implementation can account for the data better than a deterministic implementation and is also more robust. Our results demonstrate that differences between experimental results obtained in hippocampus and visual cortex can be accounted for by the different synaptic and dendritic dynamics in these two systems.     

Long-term potentiation of synaptic transmission in kitten visual cortex

1. Potentiation of synaptic transmission in visual cortex (areas 17 and 18) of kittens was investigated by extracellular recording of field potentials (FPs) and cortical units in cortical slices and whole-animal preparations. Responses to test stimulation (0.05 Hz) of the white matter (WM), lateral geniculate nucleus (LGN), and optic chiasm (OC) were documented before and after conditioning stimulation (2 Hz for 1 h). 2. In slice preparations of area 17, the FPs were always depressed during conditioning stimulation and were usually potentiated immediately after conditioning stimulation. Long-term potentiation (LTP) of FPs developed rapidly during the initial 1-2 h and continued to increase slowly for several hours after conditioning. 3. LTP of FPs was age dependent: LTP occurred most frequently (43/53) at the ages of 21-34 days, less frequently (4/7 and 5/11) at 14-20 and 35-41 days, and never (0/5 and 0/5) at 7-13 and 42-49 days. LTP age relationship determined as a ratio of the amplitudes of FPs after conditioning to that before conditioning was greater at 21-34 days (mean potentiation, 2.4 +/- 0.6) than at 14-20 or 35-41 days (1.7 +/- 0.5). 4. LTP was also documented by the shortening in latencies of orthodromic responses of cortical units sampled from 10 pairs of conditioned and unconditioned control slices. Unit responses were classified into mono- and polysynaptic groups according to the central delay, defined as the time required for their activation after the arrival of afferent impulses. The monosynaptic central delays were 0.22 ms shorter in conditioned (0.60 +/- 0.17 ms, n = 56) than in control slices (0.82 +/- 0.22 ms, n = 57); similarly, polysynaptic central delays were 0.66 ms smaller (1.70 +/- 0.43 ms, n = 51; and 2.36 +/- 0.79 ms, n = 51). Both differences were statistically significant (P less than 0.001). 5. There were laminar differences in LTP of mono- and polysynaptic transmission. LTP of monosynaptic transmission occurred throughout layers II-V (central delays shortened about 0.2 ms), whereas LTP of polysynaptic transmission was greatest in layer II (1.17 ms), moderate in layer III (0.66 ms), and slight in layer IV (0.3 ms). The time course of shortening in orthodromic latency in five polysynaptic units agreed with the time course of LTP of FP. 6. Location of synapses involved in LTP of synaptic transmission was studied by current source-density (CSD) analysis in slice preparations of area 17 during test stimulation of WM. CSD analysis demonstrated two components of current sinks (early and late), probably representing mono- and polysynaptic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)     

Changes of drebrin expression in the visual cortex of the cat during development.

The expression of and developmental changes in drebrin were studied in cat visual cortex using immunohistochemistry and immunoblot analysis. Drebrin is a developmentally regulated brain protein which in the chicken has characteristic changes in expression related to developmental stage. A monoclonal antibody (MAb M2F6) raised against drebrin, was found to label the neuropil of the kitten visual cortex in the early postnatal period. At 1-3 weeks of age, the staining was prominent in layer IV of the visual cortex. The immunoreactivity, however, was found to be dramatically decreased around the end of the sensitive period for ocular dominance plasticity (approximately 3 months of age). In the adult visual cortex, almost no immunostaining was observed. These developmental changes revealed by an immunohistochemical method were confirmed using immunoblot analysis. Upon immunoblot analysis after SDS-PAGE of protein from the kitten visual cortex, MAb M2F6 was found to recognize two protein bands with molecular weights of 130 kDa (drebrin E) and 140 kDa (drebrin A). The developmental profile of the intensity of the two bands of the drebin closely parallels in time the postnatal changes in cortical susceptibility to visual deprivation. These results indicate that the expression of drebrin in kitten visual cortex is restricted to the early postnatal period and suggest that it may play an important role in the experience-dependent modification of cortical circuitry during the sensitive period.     

Orientation-selective adaptation to first- and second-order patterns in human visual cortex

Second-order textures-patterns that cannot be detected by mechanisms sensitive only to luminance changes-are ubiquitous in visual scenes, but the neuronal mechanisms mediating perception of such stimuli are not well understood. We used an adaptation protocol to measure neural activity in the human brain selective for the orientation of second-order textures. Functional MRI (fMRI) responses were measured in three subjects to presentations of first- and second-order probe gratings after adapting to a high-contrast first- or second-order grating that was either parallel or orthogonal to the probe gratings. First-order (LM) stimuli were generated by modulating the stimulus luminance. Second-order stimuli were generated by modulating the contrast (CM) or orientation (OM) of a first-order carrier. We used four combinations of adapter and probe stimuli: LM:LM, CM:CM, OM:OM, and LM:OM. The fourth condition tested for cross-modal adaptation with first-order adapter and second-order probe stimuli. Attention was diverted from the stimulus by a demanding task at fixation. Both first- and second-order stimuli elicited orientation-selective adaptation in multiple cortical visual areas, including V1, V2, V3, V3A/B, a newly identified visual area anterior to dorsal V3 that we have termed LO1, hV4, and VO1. For first-order stimuli (condition LM:LM), the adaptation was no larger in extrastriate areas than in V1, implying that the orientation-selective first-order (luminance) adaptation originated in V1. For second-order stimuli (conditions CM:CM and OM:OM), the magnitude of adaptation, relative to the absolute response magnitude, was significantly larger in VO1 (and for condition CM:CM, also in V3A/B and LO1) than in V1, suggesting that second-order stimulus orientation was extracted by additional processing after V1. There was little difference in the amplitude of adaptation between the second-order conditions. No consistent effect of adaptation was found in the cross-modal condition LM:OM, in agreement with psychophysical evidence for weak interactions between first- and second-order stimuli and computational models of separate mechanisms for first- and second-order visual processing.