The cochlear nucleus (CN), as the first brain centre in the auditory system is responsible for sorting the neural signals received from the cochlea, into parallel processing streams for transmission to the assorted higher auditory nuclei. A commissural connection formed between cochlear nuclei through direct projections, thereby provides the first site in the central auditory system at which binaural information is able to influence the ascending auditory signal. This thesis investigates the nature of commissural projections and the impact of their input upon neurons of the ventral CN (VCN) through in vivo intracellular and extracellular electrophysiological recordings together with both acoustic and electrical stimulation of the contralateral CN.

Bakgrund: Nervus medianus är armens mittersta nerv med både efferenta och afferenta nervfibrer. För att undersöka perifera nerver används neurografi. N. medianus sensorik går att undersöka både ortodromt och antidromt där den antidroma metoden framförallt används vid karpaltunnelsyndromfrågeställning. Vanligtvis stimuleras nerven då 7 respektive 14 cm från registreringspunkten på digitorum III, men det finns fördelar med att istället för 7 cm-punkten använda sig av proximal stimulering ovanför armvecket. För denna metod finns dock ont om referensvärden. Syftet med denna studie var därför att samla in referensvärden för latenstider och amplituder.  Metod: Försökspersonerna bestod av 34 personer mellan 22 och 65 år. N. medianus undersöktes sensoriskt med proximal stimulering och registrering på dig III med både 0,1 och 0,2 ms impulsduration.  Resultat: Peaklatenstider varierade mellan 5,94 och 8,7 ms (x̄=7,00 ms) och amplituder varierade mellan 7,2 𝜇V och 72,6 𝜇V (x̄=35,6) vid 0,1 ms impulsduration. Det fanns ett signifikant bidrag av både längd och ålder på både latenstider och amplituder och en signifikant könsskillnad mellan män och kvinnor kunde uppmätas. Det fanns en signifikant, men mycket liten, skillnad i latenstid för impulsduration, men inga skillnader i amplituder. Variationskoefficienten för tre upprepade mätningar varierade mellan 0,9 och 5,3 % för peaklatens och 1,0 och 15,6 % för amplitud.  Slutsats: Hos friska försökspersoner ses en viss variation för amplituder medan latenstider ligger mer samlat. Ålder och längd bör tas med i beräkning av individuella normalvärden och en könsaspekt kan inte heller uteslutas. Impulsduration bör inte ha någon klinisk relevans. Reliabiliteten är bättre för latenstider än amplituder. / Background:. Sensory nerves can be examined both orthodromic and antidromic with nerve conduction studies. In the mixed median nerve is the antidromic method mainly used for evaluation of carpal tunnel syndrome. Usually the nerve is stimulated 7 and 14 cm from the recording at digitorum III, but there are some advantages in changing the 7 cm stimulation point to a more proximal one. The purpose of this study was to collect reference values for peak latency times and amplitudes with a proximal stimulation.  Methods: 34 test subjects in the age of 22-65 years were recruited for the study. Sensory nerve conduction studies of the median nerve with proximal stimulation and recording at digitorum III were performed with both 0,1 and 0,2 ms stimulus duration.  Results: Latency times varied between 5,94 and 8,7 ms (x̄=7,00 ms) and amplitudes varied between 7,2 𝜇V and 72,6 𝜇V (x̄=35,6) when 0,1 ms stimulus duration was used. There was a significant contribution by both length and age on latency times and amplitudes and a significant sex difference. There was a small difference in latency times by stimulus duration, but not in amplitudes. The coefficient of variation varied between 0,9 and 5,3 % for peak latency time and 1,0 and 15,6 % for amplitude.  Conclusion: There was some variation in amplitudes, but the latency times were more gathered together. Age and length have to be taken in consideration while individually reference values are calculated and a sex difference cannot be ruled out. Stimulus duration probably does not have a clinically relevant impact. The reliability is better for latency times than for amplitudes.

L’excès de synchronisation dans le réseau cortico-sous-cortical est une caractéristique majeure de la maladie de Parkinson. La stimulation cérébrale profonde (DBS) à haute fréquence (HF) des ganglions de la base modifie ces synchronies et améliore significativement les troubles moteurs. Il n’était pas encore connu si l’excès de synchronisation dans le cortex moteur primaire (M1) est présent avant les signes moteurs et si la modulation antidromique des réseaux corticaux via la stimulation HF de la voie hyperdirecte cortico-subthalamique suffit à le désynchroniser. Nous avons étudié la synchronisation des activités spontanées dans M1 de souris juvéniles PINK1 -/-, modèle génétique de Parkinson (PARK6) par imagerie calcique bi-photonique in vitro et l’avons comparée à celle de souris contrôle (P14-P16). Nous avons testé l’impact de la stimulation HF des fibres cortico-subthalamiques (région subthalamique) sur ces synchronies corticales. A un stade précoce, les réseaux M1 présentent un excès de synchronisation et, dans notre modèle de tranche, la DBS HF normalise le patron de synchronisation, plaidant pour un rôle primordial de la modulation antidromique de l’activité corticale via la voie hyperdirecte. En conclusion, nous proposons, grâce à ce modèle génétique progressif, que (1) des activités de réseau pathologiques sont présentes dans M1 bien avant les premiers signes moteurs et (2) que la modulation par voie antidromique de ces réseaux corticaux est un mécanisme essentiel d’action de la DBS HF. Ces résultats montrent qu’une pathologie dégénérative est détectable très tôt dans le développement (neuroarchéologie) mais ne s’exprimer somatiquement que tardivement. / The excess of synchronization of neuronal activities within the cortico-basal ganglia network is a hallmark of the pathophysiology of Parkinson’s disease. High frequency deep brain stimulation (DBS) applied to various basal ganglia nuclei dampens the synchronized activity in the whole network, and brings about a significant motor improvement. However it is not to date established whether an early presymptomatic abnormal pattern of synchronization is present in the primary motor cortex long before motor signs, nor whether its antidromic modulation via the hyperdirect cortico-subthalamic pathway is sufficient to remove its excess of synchronization. To answer these questions we studied the synchronization of spontaneous activities in the primary motor cortex of PINK-/- mice (genetic rodent model of Parkinson’s (PARK6), a progressive model) and compared it with age-matched control mice (P14-16 (wild-type)) by means of two-photon calcium imaging. Secondly, we analyzed in vitro the impact of the high frequency stimulation of cortico-subthalamic fibers on the pattern of synchronization of cortical networks. We show that, (1) at an early stage of development, there is an excess of synchronized activity in primary motor cortical networks and that, (2) antidromic modulation of cortical activity is a key mechanism to account for the normalization of hyper synchronized activity. These results show that a neurodegenerative adult pathology may begin early during development (neuroarcheology) though clinical signs appear late in adulthood. Moreover, antidromic invasion of a network seems to be a key mechanism of deep brain stimulation.