There is ample experimental evidence describing changes of tonotopic organisation in the auditory cortex due to environmental factors. In order to uncover the underlying mechanisms, we designed a large-scale computational model of the auditory cortex. The model has up to 100 000 Izhikevich's spiking neurons of 17 different types, almost 21 million synapses, which are evolved according to Spike-Timing-Dependent Plasticity (STDP) and have an architecture akin to existing observations. Validation of the model revealed alternating synchronised/desynchronised states and different modes of oscillatory activity. We provide insight into these phenomena via analysing the activity of neuronal subtypes and testing different causal interventions into the simulation. Our model is able to produce experimental predictions on a cell type basis. To study the influence of environmental factors on the tonotopy, different types of auditory stimulations during the evolution of the network were modelled and compared. We found that strong white noise resulted in completely disrupted tonotopy, which is consistent with in vivo experimental observations. Stimulation with pure tones or spontaneous activity led to a similar degree of tonotopy as in the initial state of the network. Interestingly, weak white noise led to a substantial increase in tonotopy. As the STDP was the only mechanism of plasticity in our model, our results suggest that STDP is a sufficient condition for the emergence and disruption of tonotopy under various types of stimuli. The presented large-scale model of the auditory cortex and the core simulator, SUSNOIMAC, have been made publicly available.

• Keywords
• Auditory cortex, Large-scale model, Oscillation, STDP, Spiking neuron, Tonotopy,
• MeSH
• Action Potentials physiology   MeSH
• Acoustic Stimulation MeSH
• Humans MeSH
• Models, Neurological * MeSH
• Nerve Net physiology   MeSH
• Neurons physiology   MeSH
• Computer Simulation * MeSH
• Auditory Cortex cytology   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In the present study, an unbiased stereological method was used to determine the number of all neurons in Nissl stained sections of the inferior colliculus (IC), medial geniculate body (MGB), and auditory cortex (AC) in rats (strains Long Evans and Fischer 344) and their changes with aging. In addition, using the optical fractionator and western blot technique, we also evaluated the number of SMI-32-immunoreactive (-ir) neurons and levels of non-phosphorylated neurofilament proteins in the IC, MGB, AC, and visual cortex of young and old rats of the two strains. The SMI-32 positive neuronal population comprises about 10% of all neurons in the rat IC, MGB, and AC and represents a prevalent population of large neurons with highly myelinated and projecting processes. In both Long Evans and Fischer 344 rats, the total number of neurons in the IC was roughly similar to that in the AC. With aging, we found a rather mild and statistically non-significant decline in the total number of neurons in all three analyzed auditory regions in both rat strains. In contrast to this, the absolute number of SMI-32-ir neurons in both Long Evans and Fischer 344 rats significantly decreased with aging in all the examined structures. The western blot technique also revealed a significant age-related decline in the levels of non-phosphorylated neurofilaments in the auditory brain structures, 30-35%. Our results demonstrate that presbycusis in rats is not likely to be primarily associated with changes in the total number of neurons. On the other hand, the pronounced age-related decline in the number of neurons containing non-phosphorylated neurofilaments as well as their protein levels in the central auditory system may contribute to age-related deterioration of hearing function.

• Keywords
• SMI-32, aging, auditory system, neurofilaments, number of neurons,
• Publication type
• Journal Article MeSH

The inferior colliculus (IC) plays a strategic role in the central auditory system in relaying and processing acoustical information, and therefore its age-related changes may significantly influence the quality of the auditory function. A very complex processing of acoustical stimuli occurs in the IC, as supported also by the fact that the rat IC contains more neurons than all other subcortical auditory structures combined. GABAergic neurons, which predominantly co-express parvalbumin (PV), are present in the central nucleus of the IC in large numbers and to a lesser extent in the dorsal and external/lateral cortices of the IC. On the other hand, calbindin (CB) and calretinin (CR) are prevalent in the dorsal and external cortices of the IC, with only a few positive neurons in the central nucleus. The relationship between CB and CR expression in the IC and any neurotransmitter system has not yet been well established, but the distribution and morphology of the immunoreactive neurons suggest that they are at least partially non-GABAergic cells. The expression of glutamate decarboxylase (GAD) (a key enzyme for GABA synthesis) and calcium binding proteins (CBPs) in the IC of rats undergoes pronounced changes with aging that involve mostly a decline in protein expression and a decline in the number of immunoreactive neurons. Similar age-related changes in GAD, CB, and CR expression are present in the IC of two rat strains with differently preserved inner ear function up to late senescence (Long-Evans and Fischer 344), which suggests that these changes do not depend exclusively on peripheral deafferentation but are, at least partially, of central origin. These changes may be associated with the age-related deterioration in the processing of the temporal parameters of acoustical stimuli, which is not correlated with hearing threshold shifts, and therefore may contribute to central presbycusis.

• Keywords
• GABA, aging, calbindin, calretinin, inferior colliculus, parvalbumin, rat,
• Publication type
• Journal Article MeSH