Local Circuit Functions

Whereas the basic structure of neocortex involves five layers of neurons and one layer of fibers that differ in functional role, neuron types, and connections, the functioning of the cortex cannot be fully understood from this framework alone. It is also important to consider several additional features of cortical organization. First, all layers of cortex contain populations of two fundamentally different types of neurons. The ones discussed so far excite each other and use the excitatory neurotransmitters. The release of an excitatory neurotransmitter at each synaptic contact tends to depolarize the contacted neuron and increase the probability of an action potential and the transmission of information. These excitatory pyramidal and spiny stellate cells constitute roughly 80% of the total number of neurons. The other 20% of neurons, distributed across the layers, are nonspiny stellate cells that release the inhibitory neurotransmitter, GABA, which hyperpolarizes the contacted neuron and decreases the probability of an action potential. The GABAergic or inhibitory neurons in the cortex all have short axons that distribute locally, and thus they are considered to be interneurons or local circuit neurons (Fig. 2). Inhibitory and excitatory neurons interact to produce important outcomes within the circuitry of neocortex. First, circuits tend to respond briefly to changes in input. Input to layer 4 excites both excitatory and inhibitory neurons. The excitatory neurons transmit excitation to other excitatory and inhibitory neurons. The inhibitory neurons inhibit excitatory neurons and other inhibitory neurons. The immediate result is to limit the duration times of a cortical response to any input. The initial excitation gets through to activate the neuron, but later arriving inhibition dampens subsequent activity. Thus, the system selectively responds to what is new and changing in time. Response to temporal changes in the environment is usually what is significant for adaptive behavior and survival. Second, circuits compare and contrast adjacent inputs. The synaptic contacts of inhibitory neurons are local, and they tend to distribute horizontally to adjacent neurons. Thus, when adjacent vertical arrays of neurons respond to the same stimuli, they tend to inhibit each other and overall excitation decreases. In contrast, if input to adjacent neurons is activated by different stimuli so they do not respond at the same time, less lateral inhibition occurs to dampen local excitation. The circuits of neurons are most excited by local differences in activating input that is often related to spatial contrast in the stimuli falling on the retina, skin, or cochlea. Spatial antagonism between a core of neurons and a surround of neurons provides a neural mechanism for emphasizing spatial differences over uniformity, again something that is very useful biologically. A fly on a sheet of paper, for example, activates cortical neurons more than any comparable location on the uniformly white sheet of paper, and we easily detect the fly. By repeating neural computations in a series of successive circuits, the temporal and spatial contrast detection features of circuits can progress from local to global features and from mediating simple and "mindless" abilities to the complex and astonishing.

What else is important about neural circuits in the neocortex? Local circuits in vertical arrays in neocor-tex interact with each other within each area over short, lateral, or horizontal connections. Excitatory neurons, especially in layer 3, often have horizontal connections extending for several millimeters within the layer. The existence of these connections, which are relatively sparse, has long been known, but their significance is only now beginning to be understood. Basically, it appears that these sparse and relatively weak connections correlate the ongoing activities of separate groups of neurons. If the neurons are already responding to something, it does not take much in the way of interconnections to shift the times of neuronal action potentials or spikes so that the spikes occur in the separated neurons at the same time. If some of these neurons project to the same group of neurons in another structure, the arrival of these spikes from different groups of coactive neurons at the same time will have a powerful activating effect on the target neurons. There may be many uses for such correlated firing of neurons. One suggestion is that such correlation mediates "perceptual binding." All of the neurons firing at once, being activated by different aspects of the same stimulus object, signal by their correlation that they are responding to the same object. The object is thereby seen as one whole, rather than as fragments.

Another feature of neocortex that makes it so biologically useful is that the circuits are adjustable, rather than fixed. They are adjusted by "experience" in the way they respond to stimuli and other neurons so that they function in more useful and productive ways. This is largely because neurons have two types of membrane receptors for the excitatory neurotransmit-ter, glutamate. One type of receptor, the non-NMDA receptor functions as an excitatory channel that tends to generate neuronal spikes. The other receptor, the N-methyl-D-aspartate or NMDA receptor, is often blocked by a magnesium ion at resting membrane potentials so that glutamate release has no effect and the NMDA receptor fails to participate in the neuron's response. However, when the neuron has been depolarized by the activation of the non-NMDA receptors, the magnesium ion is released and the NMDA receptors can be activated and pass calcium ions by glutamate release, but only for a small fraction of a second. In some sense, the receptors function as "coincidence" detectors, because they are active when two sources of excitation are closely timed. The activation of NMDA receptors then provokes internal alterations in the neuron that strengthen the effectiveness of the synapses that were just active. Thus, some connections in the circuit are made more powerful. This change is often called long-term potentiation or LTP because synapses are potentiated or strengthened for up to weeks at a time. Other activity patterns weaken synapses. This change is called long-term depression or LTD. Thus, local circuits of neurons are always being altered in activity-dependent ways. These alterations are important in shaping brain circuits during development and throughout life. They adjust the performance of local circuits and are necessary responsible for learning from sensory experience.

Neocortex has another way of adjusting its performance. Besides excitatory and inhibitory connections input exists that releases more long-lasting neuro-transmitters that alter the probability of neurons producing spikes. Neural circuits in the neocortex do not always function at the same level of excitability. When we are drowsy or sleeping, the circuits may be harder to activate. When we are alert and motivated, the circuits may respond more readily. When we focus our attention, some groups of circuits become more responsive and others less responsive. These adjustments need not be spatially nor temporally precise, and they are mediated by neuromodulatory systems that project from the brain stem to the cortex in a widespread but regionally variable manner. When they are activated, these fiber systems release such transmitters as norepinephrine, dopamine, serotonin, or acetylcho-line. Such releases generally alter the responsiveness of cortical neurons to create greater outputs. These increases in neural activity patterns also promote longer lasting alterations of neural circuits. Acetylcho-line release, for example, is associated with arousal, and it promotes LTP and allows circuits to be modified more easily, thus improving learning during arousal.

In addition to these brain stem modulating projections that distribute broadly especially to the outer layers of cortex, some of the thalamic input also appears to be of the modulating type in that it avoids layer 4 neurons and instead terminates in the outer cortical layers, including layer 1. Such terminations, often on the distal dendrites of neurons, have only minor excitatory effects that add to the major sources of activation. The functions of such modulation are not well-understood, but they certainly add to the functional flexibility of the cortex.

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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