Métodos de análisis para la determinación de BZ3 y MBC, y

The sensory system supplies information from peripheral receptors to the brain, which processes the data at a variety of levels of complexity. The peripheral receptors are analogous to analogue-to-digital converters (ADCs), in that data from the external world, being generally grouped as visual, auditory, somatosensory, gustatory and olfactory, must be collected and then converted into a signal that can be processed within the brain. Often each receptor organ responds to an aspect of the input, such as a colour of the light spectrum or modality of touch, such as temperature, and also have an area of sensitivity, known as a receptive field, within which an appropriate stimulus will result in activation of neurons.

The neurons carrying signals from sensory receptors are afferent neurons of thePNS. These neurons project to theCNS, typically either to spinal cord ganglia or nuclei, brain- stem nuclei, or other subcortical targets, such as thalamic nuclei, and often via a series of targets. At some point along a neuron’s final projection to the cortex it is common for the neurons to cross over, or decussate, to the contralateral side of the cortex, although this is not a ubiquitous behaviour.

The final target of ascending sensory neurons are to, varyingly discretised, often topo- graphical, areas of the cerebral cortex. For example, the rat’s somatosensory area lies in the parietal region of the cortex, while the visual cortex lies in a separate area in the oc- cipital region of the cortex. The topography of the human cortex is most often associated with work of the neurosurgeon Wilder Penfield, who identified and mapped the primary motor cortex, which, similar to the primary somatosensory cortex, also has a topograph- ical map. In the mid-20th century, Penfield and Boldrey, while undertaking operations in order to alleviate patients’ epileptic symptoms, were stimulating various areas of the cortex to identify vital ones that should not be removed. During this process, Penfield and Boldrey discovered that stimulations applied to the precentral gyrus, also known as the motor strip, resulted in highly localised muscle contractions on the contralateral side of the body, and in addition to this that there was a somatotopic representation of the

V2M V1 V2L A1 LT LN UN UT O1 M2 _M1 S1 Hindlimb Forelimb Lowe r Jaw Face and Vibrissae Dysgr anul ar Cor tex Upper Jaw _S2 PM PV PR Face Face Limbs Limbs

Figure 1.4: Lateral view of the rat’s cortical areas and their topography. The primary

somatosensory cortex (S1) has a body representation, the ratunculus, which has finer representations for the paw digits and the large vibrissae. S1 is surrounded by association cortices: the secondary somatosensory cortex (S2), dysgranular cortex, and the parietal- ventral (PV), parietal-medial (PM), and parietal-rostral (PR) areas. The S2 and PV regions have additional body maps. The primary visual cortex (V1), and medial and lateral secondary visual cortices (V2M and V2L) also have a topography. Only a coarse retinotopic map of the visual field is shown for V1: upper and lower temporal (UT and LT), and upper and lower nasal (UN and LN). Also shown are the primary motor cortex (M1), secondary motor cortex (M2), auditory cortex (A1), and olfactory cortex (O1). Modified from Kaas (2009)[93]_{, with permission from Elsevier.}

corresponding parts of the body[91]_{. The same topography has been found in the rat} somatosensory cortex, and whilst the discovery of Penfield and Boldrey was termed the motor homunculus, the rat’s equivalent is the ratunculus (Figure 1.4). Such topogra- phy has also been identified in the visual cortex and this is referred to as retinotopy; the retinotopic map reveals different neuronal populations responding to different portions of the visual field. The afferents supplying these areas typically arise from topographically organised sources, although there are also non-topographical areas: noradrenergic cells of the locus coeruleus, serotoninergic cells of the midbrain, cholinergic cells of the basal forebrain, and in dopaminergic cells of the midbrain. The non-topographically arranged areas projecting to the cortex may have a role in controlling cortical excitability, arousal and consciousness[92].

Despite the elegant simplicity of the topographical maps, they are not fixed in their layout, with the ability of the cortex to rearrange, known as plasticity, being an impor- tant consideration. Although the main topographic features are found to be common to all animals, cutaneous map configuration and areal extent vary substantially across individuals; early developmental experience refines and consolidates cortical functional organization. However, such reorganisation can also occur in later life; in a study by Coq and Xerri it was highlighted how, in the rat forepaw cortical region, cortical maps are con-

tinuously in use-dependent flux, with environmental enrichment refining the topography, but also increasing sensitivity[94]. There have been similar findings of inter-individual topographical variation in other cortical areas, such as the whisker representation[95], and in other species.

The traditional view is that these primary areas, such as primary somatosensory cortex (S1) and primary visual cortex (V1), then send projections to association cortices, such as secondary somatosensory cortex (S2) and secondary visual cortex (V2), which are typically numbered in an ascending fashion. This has led to a view of the nervous system and cortical processing as a hierarchical, or feed-forward, system, but, although this is in part true, the system has more complex connections. For example, often different systems integrate in a more lateral, rather than hierarchical, fashion, and connections from the cortex to subcortical areas, via feedback projections, occur. The importance of this is clear from a series experiments by Kulics et al. where monkeys were trained to report the intensity of a stimulus through the use of a button press. It was determined that the first negative-going evoked potential component (N1), which reflects signalling betweenS1andS2, correlated best with behavioural reports of the sensation, that is belief of a weak stimulus resulted in a smaller N1 signal, and vice versa, and this correlated to the chosen action[96]. This reflects the situation that cortical hierarchy is not strictly serial, and rather primary areas depend on higher areas as secondary input for priming and predictive mechanisms.

The reality is that both serial labelled-line processing, where each receptor signal is transmitted through a chain of relays without cross-talk, and integrative parallel process- ing occur. Labelled-line processing provides the advantage in the somatosensory system of a stimulus conveying information of the exact location of the input[97]. Nonetheless, around 70 % of cortical synapses result from intracortical connections between cortical cells. This high level of integrative, self-connectivity is almost certainly responsible for the high level of sensory processing and plasticity possible in the cortex[98]. Similarly, feedback has an important role in the sensory system; the ability to make fine tactile discriminations or to ignore somesthetic information in certain situations is facilitated by cortical feedback projections, these modulate the feed-forward transmission of tactile information at each level of the somatosensory system[99].